Patent GB-1204804-A (GB)
Title: A process for the preparation of pyrroline derivatives
IPC: C07D207/38
Filed: 1968-02-26
Abstract: 1,204,804. Pyrroline derivatives. F. HOFFMANN-LA ROCHE & CO. A.G. 26 Feb., 1968 [27 Feb., 1967], No. 56314/69. Divided out of 1,204,803. Heading C2C. [Also in Division A5] The invention comprises processes for the preparation of pyrroline derivatives and H- tautomers thereof and acid addition salts of the Formulµ I and Ia wherein R<SP>1</SP> is phenyl, C 1-7  alkylphenyl, C 1-7  alkoxyphenyl, or halophenyl, R<SP>2</SP> is phenyl, C 1-7  alkylphenyl, C 1-7  alkoxyphenyl, halophenyl, C 4-7  cycloalkyl or C 4-7  cycloalkenyl and R<SP>3</SP>, R<SP>4</SP>, R<SP>5</SP> and R<SP>6</SP> each are C 1-7  alkyl and wherein the broken lines denote that the groups attached thereby are optional, and the novel compounds of the above Formulµ I and Ia, where R<SP>1</SP> to R<SP>5</SP> is defined as above, provided that when R<SP>1</SP> and R<SP>2</SP> each are phenyl and R<SP>5</SP> and R<SP>6</SP> are both absent, at least one of R<SP>3</SP> and R<SP>4</SP> is present and when only one of R<SP>3</SP> and R<SP>4</SP> is present the alkyl group denoted thereby contains at least 2 carbon atoms. The processes are as follows:- (a) treating an isocyanate of the general formula with an alkaline reagent or (b) treating a dinitrile of the general formula with a reducing agent or (c) hydrolysing the corresponding 2-alkoxycarbonyliminopyrrolidine or 2-alkoxycarbonylamino-#<SP>1</SP>-pyrroline with an alkaline reagent or (d) treating the corresponding 2-amino-#<SP>1</SP>- pyrrolinone-(5) with a reducing agent or (e) treating a bromonitrile of the general formula with ammonia and, if desired, converting the resulting product into an acid addition salt. The following intermediates are prepared:- 2 - ethoxycarbonylimino - 3,3 - diphenyl - 5 - methyl - pyrrolidine, dimethyl - 2 - (dimethylaminomethyl) - 2 - ethylmalonate hydrochloride and the free base, dimethyl 2-trimethylammoniummethyl - 2 - ethylmalonate iodide, dimethyl 2 - ethyl - 2 - (2,2 - diphenyl - 2 - cyanoethyl) - malonate, 2 - ethyl - 4 - cyano - 4,4 - diphenylbutyric acid, and the acid chloride thereof, 3,3-diphenyl- 3 - cyano - 1 - ethylpropyl isocyanate, ethyl 2 - butyl - 4 - cyano - 4,4 - diphenylbutyrate, 2 - butyl - 4 - cyano - 4,4 - diphenylbutyric acid, 3,3 - diphenyl - 3 - cyano - 1 - butylpropyl isocyanate, 2 - isobutyl - 4 - cyano - 4,4 - diphenylbutyric acid, 3,3 - diphenyl - 3 - cyano - 1 - isobutylpropyl isocyanate, 2 - hexyl - 4 - cyano - 4,4 - diphenylbutyric acid, 3,3-diphenyl-3-cyano-1-hexylpropyl isocyanate, 2 - phenyl - 2 - [cyclohexen - (1) - yl] - 4 - bromobutyronitrile, 2 - ethoxycarbonylamino- 3,3 - diphenyl - 4,4 - dimethyl - #<SP>1</SP> - pyrroline, 2,2- dimethyl - 3,3 - diphenyl - 3 - cyanopropionic acid chloride and amide, 2-amino-3,3-diphenyl-4,4- dimethyl - #<SP>1</SP> - pyrrolinone - (5), 2 - phenyl - 2 - paratolyl - 4 - bromobutyronitrile, 2 - methyl - 3,3 - diphenyl - 3 - cyanopropionic acid chloride and amide, 2 - amino - 3,3 - diphenyl - 4 - methyl - #<SP>1</SP> - pyrrolinone - (5), methyl 3 - cyano - 3,3 - diphenyl - 2 - butylpropionate, 3 - cyano - 3,3 - diphenyl - 2 - butylpropionic acid, acid chloride, and acid amide, and 2-amino-3,3-diphenyl-4- butyl-#<SP>1</SP>-pyrrolinone-(5)