GB657302A - Improvements in and relating to the preparation of substituted aralkanolamine and derivatives thereof - Google Patents

Abstract

Amines of the formula <FORM:0657302/IV (b)/1> (in which R1 is an aryl group which may be substituted by alkyl or alkoxy groups, R2 and R3 are hydrogen atoms or an alkyl radical, R4 is hydrogen, R5 is hydrogen or an alkyl radical and R6 and R7 may be the same or different alkyl, alkenyl or aralkyl groups or -NR6R7 may be a pyrrolidino-, morpholino- or piperidino group) are prepared by treating with one another the corresponding b -aminoethyl aryl ketone or a salt thereof and the appropriate alkyl magnesium halide or organo-lithium compound and hydrolysing the organometallic compound produced. The reaction is preferably carried out in an anhydrous mutual solvent by allowing to stand or by heating until reaction is complete. The product is hydrolysed, suitably by addition of water followed by acetic acid, to give a salt of the base, which, if insoluble, may be separated by filtration and converted to the free base by treating with aqueous alkali, or if soluble in the reaction mixture, is basified with aqueous alkali, and extracted with an organic solvent which is subsequently evaporated. The 3-aryl-3-hydroxy alkyl tertiary amines formed may be converted into the corresponding quaternary salts by treatment with an alkyl or aralkyl halide. The quaternization may be effected in a solvent such as acetone, methanol, ethanol or dioxane. In examples the following compounds are prepared in each case by means of the Grignard reaction: (1) 1-N-piperidino-3-phenyl - nonan - 3 - ol; (2) 1 - dimethylamino - 3 - phenyl - butan - 3 - ol; (3) 1 - N - piperidino-3 - phenyl - 4 - methyl - pentan - 3 - ol; (4) 1 - N - piperidino - 3 - phenyl - heptan - 3 - ol and its salt with methyl iodide; (5) 1-N-piperidino-3-phenyl-pentan-3-ol, and its hydrochloride; (6) 1 - N - piperidino - 3 - phenyl - hexan - 3 - ol, and its hydrochloride; (7) 1-N-piperidino-3-phenyl-octan-3-ol, and its hydrochloride; (8) 1 - N - piperidino - 3 - phenyl - decan - 3 - ol, and its hydrochloride; (9) 1-N-piperidino-3-phenylundecan-3-ol, and its hydrochloride; (10) 1-diethylamino - 3 - phenyl - octan - 3 - ol, and its hydrochloride; (11) 1-dibutylamino-3-phenylhexan-3-ol, and its hydrochloride; (12) 1-N-piperidino-3-p-tolyl-hexan-3-ol, and its hydrochloride. Specification 307,304, [Class 2 (iii)], is referred to.