Patent GB-702847-A (GB)
Title: Process for the preparation of thienyl substituted tertiary amines
Inventor: DUFFIN WALTER MARK
Filed: 1950-04-28
Abstract: Tertiary mono-amines of the general formula <FORM:0702847/IV(b)/1> wherein R1 represents hydrogen or an aryl or aralkyl group or an alkyl group which may contain an alkoxy substituent, R2 and R3 may be the same or different and are alkyl groups containing from 1 to 3 carbon atoms, or the -NR2R3 group represents the morpholino, pyrrolidino or piperidino group, R4 and R5 are thienyl groups or alkyl substituted thienyl groups, and R6 represent hydrogrogen or an alkyl group containing from 1 to 3 carbon atoms, are prepared by hydrogenating compounds of the general formula <FORM:0702847/IV(b)/2> wherein R1, R2, R3, R4 and R5 have the significance indicated above, with metallic sodium in an alcohol (preferably an alcohol having not more than 6 carbon atoms) with or without the presence of water, or in liquid ammonia, or with sodium amalgam and an acid.  In the examples the following compounds are prepared: 3-dimethylamino-1:1-di-21-thienylbutane and the hydrochloride and hydrogen oxalate salts, 3-diethylamino-, 3-ethylmethylamino-, 3-pyrrolidino- and 3-morpholino-1:1-di-21-thienylbutane and their hydrochloride salts, 3-piperidino-1:1-di-21-thienylbutane and its hydrogen oxalate salt, 3-dimethylamino- and 3-dimethylamino-2-methyl-1: 1 - di - 21-thienylpropane and their hydrogen oxalate salts, 3-dimethylamino-1:1-di-21-thienylhexane and its hydrochloride salt, 3-dimethylamino-1:1-di-21-(5-methylthienyl) butane and its hydrochloride salt, 3 - dimethylamino - 1 : 1 - di - 21 - (4-methylthienyl) butane, 3-dimethylamino-4-phenyl-1:1-di-21-thienyl-butane and its hydrochloride salt, 3-dimethyl-amino-4-methoxy-1: 1-di-21-thienylbutane and its hydrogen oxalate salt, 3-dimethyl amino-1 - 21 - (5 - methylthienyl) - 1 - 21 - thienylbutane and its hydrochloride salt and 3-dimethylamino - 1 - 21 - (4 - methylthienyl)-1 - 21 - thienylbutane.  Specifications 657,301, 702,269 and 702,827 are referred to. 2-Dimethylamino-3-phenylbutyrate is prepared by the addition of dimethylamine to methyl styrylacetate. 2-Dimethylamino-3-methoxybutyrate is prepared by the addition of dimethylamine to methyl 3-methoxycrotonate.  2-b -Dimethylaminobutyrothienone is prepared by the addition of dimethylamine to 2-crotonothienone.  3-Dimethylamino - 1-21-(4-methylthienyl) - 1-21-thienybut-1-ene is prepared by dehydrating the carbinol (the hydrogen oxalate salt is also referred to) obtained from the reaction of 2-(4-methylthienyl) lithium with 2-b -dimethylaminobutyrothienone.  The hydrochloride salt is also mentioned.  Similarly  3 - Dimethylamino - 1 - 21 - (5 - methylthienyl) - 1-21-thienylbut-1-ene is prepared using 2-(5-methylthienyl) lithium.  The hydrochloride salt is also mentioned.  3 - Dimethylamino-1:1-di-21-(5-methylthienyl) - but-1-ene is prepared by the reaction of 2-(5-methylthienyl) lithium and a dimethylamino substituted butyrate and dehydrating the resulting carbinol.  The hydrochloride salt is also mentioned.  Similarly  3 - Dimethylamino-1:1-di-21-(4 - methylthienyl) but-1-ene is prepared using 2-(4-methylthienyl) lithium.  3 - Dimethylamino - 4 - phenyl 1:1 - di - 21 - thienylbut-1-ene is prepared by the reaction of 2-thienyllithium and methyl 2-dimethylamino-3-phenylbutyrate and dehydrating the resulting carbinol.  The hydrochloride salt is also mentioned. Similarly  3 - Dimethylamino - 4 - methoxy - 1 : 1 - di - 21 thienylbut-1-ene is prepared using methyl 2-dimethylamino-3-methoxy-butyrate.