Patent GB-682161-A (GB)
Title: Improvements in and relating to the preparation of substituted amino ketones and derivatives thereof
Inventor: BARRETT PAUL ANTHONY
IPC: C07D295/10
Filed: 1948-10-19
Abstract: 682,161. Substituted amino ketones and amino-alcohols and their derivatives. WELLCOME FOUNDATION, Ltd. Oct. 18, 1949 [Oct. 19, 1948], No. 27120/48. Class 2 (iii). A process for the production of substituted #-(tertiaryamino) alkyl ketones of the general formula wherein R 1  denotes an aralkyl or thienyl group or an aryl group optionally substituted by alkyl or alkoxy groups containing up to 4 carbon atoms or by halogen atoms, R 3  and R. are the same or different and each denotes an alkyl, alkenyl, cycloalkyl or aralkyl group, or R 3  and R 4  together with the adjacent nitrogen atom constitute a morpholino, pyrrolidino, piperidino or N<SP>1</SP>-alkyl-N-piperazino group and n is an integer from 3 to 10, comprises reacting an ester of the general formula where R is an alkyl group, or a salt thereof, with an organomagnesium halide of the formula R 1 MgX, where X is a halogen atom, hydrolysing the organometallic compound so formed, and separating the ketone from the reaction mixture. In some instances a carbinol of the formula is formed as a by-product. To characterize the ketones they may be converted into quarternary compounds of the general formula where R 5  is an alkyl or aralkyl radical and X- is an acid radical, e.g. the chloride, bromide, iodide or methosulphate radical. Examples describe the preparation of (1) phenyl-(3-N- piperidinopropyl)-ketone from 3-N-piperidino butyric acid ethyl ester and phenyl magnesium bromide; (2) phenyl-(3-diethylaminopropyl)- ketone from 3-diethylaminobutyric acid ethyl ester and phenyl magnesium bromide. Similarly prepared are (3) phenyl (4-N-piperidinobutyl)-ketone; (4) phenyl-(5-N-piperidinoamyl)-ketone; (5) phenyl-(8-N-piperidino-octyl) ketone; (6) phenyl-(10-N-piperidinodecyl)- ketone; (7) 1-N-pyrrolidino-7-phenylheptane- 6-one; (8) I-N-pyrrolidino-6-p-tolylhexan-6- one; (9) 1-N-pyrrolidino-6-p-methoxy-phenylhexan-6-one; (10) 1-N-methyl-N-benzylamino- 6-phenylhexan-6-one; (11) 1-cyclohexylamino- 6-phenylhexan-6-one; (12) 1-N-morpholino-6- phenylhexan-6-one; (13) phenyl-(5-diallylaminoamyl)-ketone; (14) 6-N-pyrrolidino-1- (2<SP>1</SP>-thienyl)-hexan-1-one; (15) 9-N-pyrrolidino- 1-phenylnonan-1-one; (16) 5-dimethylamino- 1-phenylpentan-1-one; (17) 5-N-pyrrolidino-1- phenylpentan-1-one; (18) 6-N-piperidino-1-pchlorophenylhexan-1-one; (19) 6-N<SP>1</SP>-methyl- N - piperazino - 1 - phenyl - hexan - 1 - one; (20) 6 - dibutylamino - 1 - phenylhexane - 1- one. The corresponding quaternary ammonium salts are prepared by reacting the products of examples 1 to 4 and 6 with methyl iodide. Carbinols obtained as by products in the above examples are: (1) 1 : 1-diphenyl-4-(1<SP>1</SP>-piperidino)-butan-1-ol; (2) 1 : 1-diphenyl-4-diethylaminobutan-1-ol; (5) 1 : 1-diphenyl-9-(1<SP>1</SP>-piperidino)-nonan-1-ol; (6) 1 : 1-diphenyl-11-(1<SP>1</SP>- piperidino)-undecan-1-ol; (13) 1 : 1-diphenyl- (6-diallylamino)-pentan-1-ol; (15) 9-N-pyrrolidino - 1 : 1 - diphenylnonan - 1 - ol. The following substituted esters are prepared as starting materials (4) 5-N-piperidino caproic acid ethyl ester from 5-bromocaproic ester and piperidine; (5) 8-piperidino nonoic acid ethyl ester from piperidine and 8-bromononoic acid ethyl ester; (6) ethyl-10-piperidino undecylate from ethyl-10-bromo-undecylate and piperidine; (7) 5-N-pyrrolidino caproic acid ethyl ester from 5-bromocaproic acid ethyl ester and pyrrolidine; (10) 5-N-methyl-N-benzylamino caproate; (11) dicyclohexylaminocaproic acid ethyl ester from 5-bromocaproic acid ethyl ester and dicyclohexylamine; (12) 5-N-morpholinocaproic acid ethyl ester from 5-bromocaproic acid ethyl ester; (16) 4-dimethylamino valeric acid ethyl ester from ethyl-4-chlorovalerate and dimethylamine; (17) 4-N-pyrrolidinovaleric acid ethyl ester from 4-bromovaleric acid ethyl ester and pyrrolidine; (19) 5-N<SP>1</SP>-methyl-N-piperazinocaproic acid ethyl ester from 5-bromocaproic acid ethyl ester and N-methylpiperazine; (20) 5-dibutylaminocaproic acid ethyl ester from 5- bromocaproic acid ethyl ester and dibutylamine. Specification 682,160 is referred to.