US2079962A - Basic esters of polyarylacetic acids and process of making the same - Google Patents

Basic esters of polyarylacetic acids and process of making the same Download PDF

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US2079962A
US2079962A US30166A US3016635A US2079962A US 2079962 A US2079962 A US 2079962A US 30166 A US30166 A US 30166A US 3016635 A US3016635 A US 3016635A US 2079962 A US2079962 A US 2079962A
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Miescher Karl
Hoffmann Karl
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FIRM OF SOCIETY OF CHEMICAL INDUSTRY IN BASLE
SOC OF CHEMICAL IND
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
    • C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
    • C07C213/06—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton from hydroxy amines by reactions involving the etherification or esterification of hydroxy groups

Definitions

  • This invention relates to the manufacture oi basic esters of polyarylacetic acids, which are compounds of considerably greater compatibility than the said ester of benzilic acid.
  • the easily accessible dialkylaminoethanol ester of diphenylacetic acid has an extraordinarily powerful effect on the unstriated mus- 2g cles. . This is unexpected, since hitherto it has been supposed that the presence of an aliphatic hydroxyl group in the acid residue (tropic acid, atrolaotic acid, atroglyceric acid, mandelic acid or benzilic acid) favored the action.
  • the new compounds may be made by acting upon polyarylacetic acids or on a halide, ester or anhydride thereof, in the presence or absence of a condensing agent, with an aminoalkanol disub stituted at the nitrogen atom, or by the action of a reactive ester of an aminoalkanol, disubstituted at the nitrogen, on a polyarylacetic acid or a salt thereof, if desired in the presence of an agent which binds acid.
  • polyarylacetic acids may be converted into their halogen- 36 alkanol esters and the latter caused to react with a secondary amine.
  • alkylene-halogen-hydrines 40 are caused to react on polyarylacetic acids or the halides, esters or anhydrides thereof, in the presence or absence of condensing agents, or that.
  • hydroxyl-group which may be present by halogen.
  • an alkyl halide an alkylene halide, an aryl sulfonic acid ester, a. dialkylsulfate, 0 an arylalkyl halide or the like, quaternary ammonium compounds of the bases in question can be produced.
  • esters of aminoalkanols are particularly included esters of these with hydrohalogen acids or arylsulfonic acids or the like.
  • the new compounds are useful for therapeutic application.
  • 10.6 are of a,a-diphenylacetic acid are treated with thionyl' chloride and the diphenylacetyl chloride thusproduced is caused to react with 5 ⁇ parts of diethylaminoethanol at C.
  • the unadiphenylacetic acid 2 (diethylamino) -ethauolesterhydrochloride of the formula CaHu V /CSEB err-comom-cm-u thus produced is recrystallized from ethyl ace-
  • Example 2 42.4 parts of diphenylacetic acid, 41 parts of chlorethyl-diethylamine-hydrochloride, 55 parts of potassium carbonate and 120 parts of acetone are together heated to boiling in a reflux apparatus until the reaction is complete.
  • the same compound may also be obtained by causing equivalent quantities of diphenylacetic acid ethylmethylor another ester to react with diethylaminoethanol in the heat, and'fractionating the reaction product in a vacuum.
  • Example 3 11.5 parts of'diphenylacetic acid chloride-are caused to react, in presence ot- 30 parts of dry'pyridine, with 6.5 parts of allylethvlaminoethanol of the formula (boiling at 172 C. at 740mm. pressure, obtained from allylbromide' and ethylaminoethanol) The product of the reaction is extracted with ether ethanol; the reaction mass is extracted with ether,
  • Example 5 23 parts of diphenylacetic acidchlorlde .are caused toreact with 8 parts of ethylenechlorohydrine in presence of pyridine. The reaction product is shaken with ether and water; the ethereal solution is dried, the solvent evaporated and the residue fractionated in a vacuum. The
  • ethylene chlorhydrine - also other ethylene halogen-hydrines, for example ethylenebromohydrinamay be used.
  • an alkali salt of the diphenylacetic acid is caused to react with an ethylenedihalide as, for instance, ethylene chlorobromide, ethylene bromide or ethylene iodide, or an ethylene halogen-hydrine is caused to react thereupon, and the hydroxyethanol ester thus obtained is treated, for instance, with thlonyl chloride.
  • diphenylacetic acid-2-methylethylaminoethanol'ester (a colorless oil of boiling point 136-138? C. at 0.015 mm. pressure) diphenylacetic acid- 2 di-n-butylaminoethanol ester (boiling point 163-l65 C. at 0.01 mm. pressure, sulfate melting point 139-140 C.) diphenylacetic acid-2- point 149-151 C.), diphenylacetic acid-meta-dimethyl aminocyclohexanol ester (viscous oils of boiling point PTO-180 C. at 0.035 mm. pressure); the orthoand para-compounds are also forming viscous oils.
  • the parent materials hitherto not known for the production of the above compounds are ob tained as follows: methylethylaminoethanol (boiling point 146-148 C. at 734 mm. pressure) from ethylaminoethanol and formaldehyde in presence of formic acid; m-dimethyl aminocyclohexanol (boiling point 101-104 C. at 6 mm. pressure) by methylating m-aminocyclohexanol of melting point 73 C., the latter being obtained by reducing m-acetylaminophenol with a catalyst and by subsequent saponification.
  • the orthoor para-compounds are obtained in an analogous manner.
  • a process for the manufacture of basic W esters which comprises causing products of the formula ⁇ C-CO can formulo wherein R represents a member of the group consisting' of hydrogen and phenyl and a: represents a member of the group consisting of oxyalkyl and halogen, toreact with products of the formula HO-CHPCM wherein 11 represents a. member of the group consisting of a dialkylamine, an alkyl-allylaniine and a. piperidine ring.
  • a process for the manufacture of basic 10 esters which comprises causing products of the formula.
  • Oc'tu GH-QOfi I 06m I 0 wherein 2 represents o mher of the gl'flup wusisting of owolml and halogen, to. react with products of the fomnuia I wherein 1/ represents a member of the group consisting of a disihwismine, an nlkyl-allylnmine and a piper-mine ring.
  • a stands for a member selected from the group consisting of onyaiky'l and halogen, to react with the product of the formula /CaHa I as Ho-cHr-cm -N Cali's l3fA'process fortlse manufacture of a basic ester, which consists in cousins products of the 40 Cum v CcHB I I V wherein's stands for a member selected from the group consisting of onyaiiryi and halogen, to react with the product of the formulas cur-on,
  • a process for the ufectnre of basic esters whichconsists in c products of the formuls CuHa wherein .2: stands for s member selected from the group consisting of oxyslkyl end halogen, to react with products of the formula wherein A stands for a, cyclohee ring and R1 and R2 stand for slksl.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Hydrogenated Pyridines (AREA)

Description

Patented May 11, 1937 PATENT orrlc BASIC ESTERS F POLYARYLACETIG ACIDS ANI) PROCESS OF MAKING THE SAME 1 Karl Miescher, Itiehen, near Basel, and Karl Hoifmann, Basel, Switzerland, assignors to the firm of Society of Chemical Industry in Basic,
Basel, Switzerland No Drawing. Application July 6, 1935, Serial No.
30,166. In Switzerland July 12, 1934 16 Claims. (01 260-43) It is known that many basic esters of tropic acid have an action similar to that of atropin, although weaker. Basic esters-of certain other organic acids also exhibit activity, for instance such 5 esters of mandelic'acid, atrolactic acid, atroglyceric acid, benzoic acid and orthoand metaoxybenzoic acid. Quite special in this respect is benzilic acid-2,2-dimethyl-S-diethyl-aminopropanol ester; its extraordinary toxic character forbids its use in the clinic (see K. Fromherz, Archiv fiir experimentelle Pathologie und Pharmakologie, 173 (1933) page 116).
This invention relates to the manufacture oi basic esters of polyarylacetic acids, which are compounds of considerably greater compatibility than the said ester of benzilic acid. Thus, for example, the easily accessible dialkylaminoethanol ester of diphenylacetic acid has an extraordinarily powerful effect on the unstriated mus- 2g cles. .This is unexpected, since hitherto it has been supposed that the presence of an aliphatic hydroxyl group in the acid residue (tropic acid, atrolaotic acid, atroglyceric acid, mandelic acid or benzilic acid) favored the action. The new compounds may be made by acting upon polyarylacetic acids or on a halide, ester or anhydride thereof, in the presence or absence of a condensing agent, with an aminoalkanol disub stituted at the nitrogen atom, or by the action of a reactive ester of an aminoalkanol, disubstituted at the nitrogen, on a polyarylacetic acid or a salt thereof, if desired in the presence of an agent which binds acid. Alternatively, polyarylacetic acids may be converted into their halogen- 36 alkanol esters and the latter caused to react with a secondary amine.
For the production of the halogen alkanol esters the operation is preferably conducted in such a manner that alkylene-halogen-hydrines 40 are caused to react on polyarylacetic acids or the halides, esters or anhydrides thereof, in the presence or absence of condensing agents, or that. al-
- kylene-halogen-hydrines or alkylene-dihalides are caused to react on salts of polyarylacetic acids,
hydroxyl-group which may be present by halogen. By the addition of an alkyl halide, an alkylene halide, an aryl sulfonic acid ester, a. dialkylsulfate, 0 an arylalkyl halide or the like, quaternary ammonium compounds of the bases in question can be produced.
Among reactive esters of aminoalkanols are particularly included esters of these with hydrohalogen acids or arylsulfonic acids or the like.
and replacing in the compounds so obtained any,
The new compounds are useful for therapeutic application.
The following examples illustrate the'invention, the parts being by weight:
Example .1
10.6 are of a,a-diphenylacetic acid are treated with thionyl' chloride and the diphenylacetyl chloride thusproduced is caused to react with 5} parts of diethylaminoethanol at C. The unadiphenylacetic acid 2 (diethylamino) -ethauolesterhydrochloride of the formula CaHu V /CSEB err-comom-cm-u thus produced is recrystallized from ethyl ace- Example 2 42.4 parts of diphenylacetic acid, 41 parts of chlorethyl-diethylamine-hydrochloride, 55 parts of potassium carbonate and 120 parts of acetone are together heated to boiling in a reflux apparatus until the reaction is complete. After cooling, the whole is filtered, the solid matter is washed with acetone and the filtrateand the washings are evaporated to dryness, the residue being extracted with ether. The etheral solution is washed with dilute sodium carbonate solution and dried over potassium carbonate The oil left on evaporating the ether is fractionated in a high vacuum.- The base thus obtained is identical with that described in Example 1.
The same compound may also be obtained by causing equivalent quantities of diphenylacetic acid ethylmethylor another ester to react with diethylaminoethanol in the heat, and'fractionating the reaction product in a vacuum.
' Example 3 11.5 parts of'diphenylacetic acid chloride-are caused to react, in presence ot- 30 parts of dry'pyridine, with 6.5 parts of allylethvlaminoethanol of the formula (boiling at 172 C. at 740mm. pressure, obtained from allylbromide' and ethylaminoethanol) The product of the reaction is extracted with ether ethanol; the reaction mass is extracted with ether,
and the ethereal solution is washed with sodium carbonate solution and dried over potassium carbonate. The solvent is then eliminated and the oil thus obtained is fractionated in a high vacuum. The diphenylacetic acid-,2-allylethylaminoethanol ester of the formula Ewample 4 30 parts of triphenylacetic acid chloride are caused to react with 24 parts of diethylam-inocal-0H1 the ethereal solution washed with dilute sodium carbonate solution and dried over potassium carbonate.- After evaporation of the solvent the triphenylacetic acid-2-diethylaminoethanol ester of the formula obtained fat 160-170 c. at 0.07 mm. pressure,vmelts at B5-90 C., and forms a hydrochloride of melting point 164-167- C., amethyliodide of melting point 223-225 C., and a methylchloride of melting point 198499 0.
Example 5 23 parts of diphenylacetic acidchlorlde .are caused toreact with 8 parts of ethylenechlorohydrine in presence of pyridine. The reaction product is shaken with ether and water; the ethereal solution is dried, the solvent evaporated and the residue fractionated in a vacuum. The
diphenylacetic acid-Z-chloro-ethanol ester of the formula CIHI oH-co'o-cm-cn,-ci
I CaHl v thus obtained boils at 130-435" 0. it-0.01 mm.
pressure. 2'1 parts of this compound are caused to react in the heat with 14 parts of diethylamine; the reaction productis shaken with ether and water; the ethereal solution'is dried and the solvent evaporated. The diphenylacetic acid-2-diethylaminoethanol ester thus obtained is identical with the substance described in Example 1 and2.
Instead of ethylene chlorhydrine -also other ethylene halogen-hydrines, for example ethylenebromohydrinamay be used.
In order to obtain the halogen-ethanol esterv used as intermediate product one can'also proacraoca.
is distilled in a high vacuum. It boils c'eed in the followlngmanner: an alkali: salt of the diphenylacetic acid is caused to react with an ethylenedihalide as, for instance, ethylene chlorobromide, ethylene bromide or ethylene iodide, or an ethylene halogen-hydrine is caused to react thereupon, and the hydroxyethanol ester thus obtained is treated, for instance, with thlonyl chloride. 1 g
In similar manner the following compounds may be obtained: diphenylacetic acid-2-methylethylaminoethanol'ester (a colorless oil of boiling point 136-138? C. at 0.015 mm. pressure) diphenylacetic acid- 2 di-n-butylaminoethanol ester (boiling point 163-l65 C. at 0.01 mm. pressure, sulfate melting point 139-140 C.) diphenylacetic acid-2- point 149-151 C.), diphenylacetic acid-meta-dimethyl aminocyclohexanol ester (viscous oils of boiling point PTO-180 C. at 0.035 mm. pressure); the orthoand para-compounds are also forming viscous oils. a
The parent materials hitherto not known for the production of the above compounds are ob tained as follows: methylethylaminoethanol (boiling point 146-148 C. at 734 mm. pressure) from ethylaminoethanol and formaldehyde in presence of formic acid; m-dimethyl aminocyclohexanol (boiling point 101-104 C. at 6 mm. pressure) by methylating m-aminocyclohexanol of melting point 73 C., the latter being obtained by reducing m-acetylaminophenol with a catalyst and by subsequent saponification. The orthoor para-compounds are obtained in an analogous manner. I
What we claim is:-'
1. The basic esters of the formula .piperidinoethanol ester (hydrochloride melting wherein Y represents a member of the group conan unsubstituted alkylene chain .and a cyclohexane ring, whichsubstances'are soluble in organic solvents and insoluble in water, forming with acids water-soluble salts of strong antispasmodic action. 2. The basic esters of the formula wherein 3 represents a member of the group consisting of a dialkylamine, an alkyl-allylamine and a pi'peridine ring, and R represents a member of the group consisting of hydrogen and phenyl,
which substances are soluble in organic solvents and insoluble in water, forming with acids watersoluble salts of strong antispasmodic action. 3. The basic esters of the formula wherein 3; represents a member of the group consisting of a dialkylamine, an alkyl-allylamine and a piperidine ring, which substances are soluble in organic solvents and insoluble in water, forming with acids water-soluble salts of strong antispasmodic action.
4. The basic ester of the formula which substance is a colorless oil soluble in organic solvents and insoluble in water, forming with acids water-soluble salts of strong antispasmodic action. i I 5. The basic ester of the formula Ccfls CHr-CE:
wherein A stones for o cyclohexane whic I substances are soluble in organic solvents and in- I soluble in water, forming with acids water-soluble soils of strong entispesmodic action. 7 8. The basic %ter of the formula w s CaHu I )QHiPGHi I CH-CQO-OH /CH$ I 00E; Clio-CH C or; i Ha which substance is a colorless oil soiubie in or-.
' genie solvents and insoluble in water, long 59 with coins weter soiuble salts of strong antispss motile action," I
9. A process for the menufacture of hassle esters, I
I which comprises causing products of the formula to Q Co s 1 wherein R, represents at member of the group con 0 sisting of hydrogen and phenyl and 3 represents s member of the group consisting of-omelkyl and halogen, to react with products of the formuio wherein A represents, 2. member of the group con sisting of an nhstituted elisylene'cn and n cyclohexene ring, and :11 represents a member of the group consisting of a diellcyiemine, memo eliylomine one, a piperldine ring. 10 A process for the manufacture of basic W esters, which comprises causing products of the formula \C-CO can formulo wherein R represents a member of the group consisting' of hydrogen and phenyl and a: represents a member of the group consisting of oxyalkyl and halogen, toreact with products of the formula HO-CHPCM wherein 11 represents a. member of the group consisting of a dialkylamine, an alkyl-allylaniine and a. piperidine ring.
11. A process for the manufacture of basic 10 esters, which comprises causing products of the formula.
Oc'tu GH-QOfi I 06m I 0 wherein 2 represents o mher of the gl'flup wusisting of owolml and halogen, to. react with products of the fomnuia I wherein 1/ represents a member of the group consisting of a disihwismine, an nlkyl-allylnmine and a piper-mine ring.
' 12. A process for the nufacture of a. basic 5 esterpwhich consists in causing products of the formula k v t I CH-C C it,
wherein a; stands for a member selected from the group consisting of onyaiky'l and halogen, to react with the product of the formula /CaHa I as Ho-cHr-cm -N Cali's l3fA'process fortlse manufacture of a basic ester, which consists in cousins products of the 40 Cum v CcHB I I V wherein's stands for a member selected from the group consisting of onyaiiryi and halogen, to react with the product of the formulas cur-on,
' cut-cu,
14. A process for the ufectnre of basic esters, whichconsists in c products of the formuls CuHa wherein .2: stands for s member selected from the group consisting of oxyslkyl end halogen, to react with products of the formula wherein A stands for a, cyclohee ring and R1 and R2 stand for slksl.
1-5. A oroce forethe nufacture of basic esters, which cc" is in cog products of the for-mule out i cn-co-e I II .4 ao'zepaa wherein z stands for'a member selected from the group consisting of oxyalkyl and halogen, to react with products of the formula r l o HOAN whez -ein A stands for a, cyclohexane ring.
whel em :1: stands fox: a. member selectea n'om the groilp consisting of oxyalkyl and halogen, to react with a. product of the formula I I CHI-CH:
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Cited By (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2415079A (en) * 1944-02-26 1947-02-04 Regents Basic-alkyl esters and their salts
US2419366A (en) * 1942-04-08 1947-04-22 American Cyanamid Co Alkanol esters
US2421729A (en) * 1943-05-20 1947-06-03 Burroughs Wellcome Co Production of 3-aryl-1, 5-dibrompentane-3-carboxylic acid
US2423025A (en) * 1942-03-31 1947-06-24 American Cyanamid Co Alkamine esters of diarylpropionic acids
US2446522A (en) * 1940-07-08 1948-08-10 Winthrop Stearns Inc Diaryl nitrogenous heterocyclic alkylene compounds
US2447395A (en) * 1940-07-05 1948-08-17 Parke Davis & Co Morpholine substituted esters
US2474651A (en) * 1944-02-26 1949-06-28 Univ Michigan Basic-alkyl esters and their salts
US2475852A (en) * 1942-04-08 1949-07-12 American Cyanamid Co Morpholinoalkanol esters
US2489950A (en) * 1944-02-26 1949-11-29 Univ Michigan Basic-alkyl esters and their salts
US2512307A (en) * 1948-07-24 1950-06-20 Sterling Drug Inc Esters of di-substituted acetic acids and sulfur containing tertiary amino alkanols
US2533084A (en) * 1946-08-17 1950-12-05 Univ Michigan Aminoalkyl esters of dithienyl aliphatic acids
US2576230A (en) * 1948-02-20 1951-11-27 Searle & Co Aminoalkyl esters of alpha, beta, beta-triarylpropionic acids
US2589937A (en) * 1947-05-23 1952-03-18 Geigy Ag J R Manufacture of new basic esters of 1-aryl-cyclopentane-1-monothiocarboxylic acids
US2607777A (en) * 1947-04-10 1952-08-19 Searle & Co N-alkyl piperidyl alkyl esters of diphenyl acetic acid and 9-fluorenyl carboxylic acid
US2648666A (en) * 1953-08-11 Quaternary ammonium salts derived
US2659725A (en) * 1950-06-21 1953-11-17 Searle & Co Quaternary ammonium salts of heterocyclylalkanol esters of xanthene-9-carboxylic acid
US2662891A (en) * 1948-01-12 1953-12-15 Schering Corp P-chlorophenyl(2-pyridyl) (beta-dimethylaminoethoxy) methane
US2918407A (en) * 1957-04-08 1959-12-22 Lakeside Lab Inc Anti-spasmodics specific for upper gastrointestinal pain and spasm
US3174994A (en) * 1962-01-30 1965-03-23 Smith Kline French Lab Hypocholesterolemic n-oxide compositions
US4767784A (en) * 1985-12-13 1988-08-30 Zoelss Gerhard Novel crystalline salts of aryloxy-propanolamines, a process for their preparation and their use
US4973734A (en) * 1989-03-17 1990-11-27 The United States Of America As Represented By The Secretary Of The Army Carbaphens: aprophen analogs that are binary antidotes for organophosphate poisoning

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DE763489C (en) * 1937-11-09 1951-08-09 Friedrich Dr Luther Process for the preparation of ª-aminoethyl esters of substituted phenylacetic acids
US2995492A (en) * 1957-12-23 1961-08-08 Lakeside Lab Inc Piperidine derivatives with psychotogenic activity
US2995560A (en) * 1959-09-11 1961-08-08 Lakeside Lab Inc Acetates of 3-piperidinol
US3014913A (en) * 1959-11-16 1961-12-26 Upjohn Co Ortho-alkanoyloxy-benzoates of n-phenylethyl-4-piperidinol
DE1163844B (en) * 1960-11-26 1964-02-27 C F Boehrm^er S. Soehne G m bH Mannheim Wildhof Process for the preparation of esters of N- (hydroxyalkyl) -nortropanes or -norgranatanes and their hydrohalides.
DE1162845B (en) * 1961-08-16 1964-02-13 C. F. Boehringer &. Soehne G.m. b.H., Mannheim-Waldhof Process for the preparation of the hydrohalides of esters of N- (hydroxyalkyl) -nortropanes or -norgranatanes.
DE1162846B (en) * 1961-08-17 1964-02-13 C. F. Boehringer & Soehne G.m. b.H., Mannheim-Waldhof Process for the preparation of esters of N- (hydroxyalkyl) -nortropanes or -norgranatanes and their salts.

Cited By (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2648666A (en) * 1953-08-11 Quaternary ammonium salts derived
US2447395A (en) * 1940-07-05 1948-08-17 Parke Davis & Co Morpholine substituted esters
US2446522A (en) * 1940-07-08 1948-08-10 Winthrop Stearns Inc Diaryl nitrogenous heterocyclic alkylene compounds
US2423025A (en) * 1942-03-31 1947-06-24 American Cyanamid Co Alkamine esters of diarylpropionic acids
US2419366A (en) * 1942-04-08 1947-04-22 American Cyanamid Co Alkanol esters
US2475852A (en) * 1942-04-08 1949-07-12 American Cyanamid Co Morpholinoalkanol esters
US2421729A (en) * 1943-05-20 1947-06-03 Burroughs Wellcome Co Production of 3-aryl-1, 5-dibrompentane-3-carboxylic acid
US2415079A (en) * 1944-02-26 1947-02-04 Regents Basic-alkyl esters and their salts
US2474651A (en) * 1944-02-26 1949-06-28 Univ Michigan Basic-alkyl esters and their salts
US2489950A (en) * 1944-02-26 1949-11-29 Univ Michigan Basic-alkyl esters and their salts
US2533084A (en) * 1946-08-17 1950-12-05 Univ Michigan Aminoalkyl esters of dithienyl aliphatic acids
US2607777A (en) * 1947-04-10 1952-08-19 Searle & Co N-alkyl piperidyl alkyl esters of diphenyl acetic acid and 9-fluorenyl carboxylic acid
US2589937A (en) * 1947-05-23 1952-03-18 Geigy Ag J R Manufacture of new basic esters of 1-aryl-cyclopentane-1-monothiocarboxylic acids
US2662891A (en) * 1948-01-12 1953-12-15 Schering Corp P-chlorophenyl(2-pyridyl) (beta-dimethylaminoethoxy) methane
US2576230A (en) * 1948-02-20 1951-11-27 Searle & Co Aminoalkyl esters of alpha, beta, beta-triarylpropionic acids
US2512307A (en) * 1948-07-24 1950-06-20 Sterling Drug Inc Esters of di-substituted acetic acids and sulfur containing tertiary amino alkanols
US2659725A (en) * 1950-06-21 1953-11-17 Searle & Co Quaternary ammonium salts of heterocyclylalkanol esters of xanthene-9-carboxylic acid
US2918407A (en) * 1957-04-08 1959-12-22 Lakeside Lab Inc Anti-spasmodics specific for upper gastrointestinal pain and spasm
US3174994A (en) * 1962-01-30 1965-03-23 Smith Kline French Lab Hypocholesterolemic n-oxide compositions
US4767784A (en) * 1985-12-13 1988-08-30 Zoelss Gerhard Novel crystalline salts of aryloxy-propanolamines, a process for their preparation and their use
US4849530A (en) * 1985-12-13 1989-07-18 Rorer Pharmaceutical Corporation Process for the preparation of crystalline salts or aryloxy-propanolamines
US4973734A (en) * 1989-03-17 1990-11-27 The United States Of America As Represented By The Secretary Of The Army Carbaphens: aprophen analogs that are binary antidotes for organophosphate poisoning

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FR795597A (en) 1936-03-17
GB448181A (en) 1936-05-25
DE680662C (en) 1939-09-06
DE626539C (en) 1936-02-27
NL42150C (en) 1937-12-15

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