GB832289A - Improvements in or relating to processes for producing substituted alkylamines and acid-addition salts thereof - Google Patents

Abstract

Compounds of the formula <FORM:0832289/IV (b)/1> and acid addition salts thereof, wherein Y1 and/or Y2 represent hydrogen atoms or hydroxyl or etherified or esterified hydroxyl groups, R1 is an alkylene or hydroxyalkylene groups of 2-6 carbon atoms and R2 is an alkylene group of 2-6 carbon atoms are made by reacting a compound of the formula <FORM:0832289/IV (b)/2> wherein R11 is an alkylene, hydroxyalkylene or keto-alkylene group of 2-6 carbon atoms, with a compound of the formula <FORM:0832289/IV (b)/3> wherein R11 is an alkylene group of 1-5 carbon atoms and X is a halogen atom or a radical <FORM:0832289/IV (b)/4> and reducing the resulting amide of the formula <FORM:0832289/IV (b)/5> by known methods for reducing the group -NH.CO- into -NH.CH2-, reducing any keto-oxygen atom present in R1 into a hydroxyl group and converting any etherified or esterified groups Y1 and/or Y2 into free hydroxyl by hydrogenation or hydrolysis, if desired. Suitably Y1 is a hydroxyl group, Y2 is hydrogen and the amide-forming reaction is carried out in a hydroxylic solvent such as an alcohol or Y1 and/or Y2 are hydrogen atoms or esterified or etherified hydroxyl groups and the reaction takes place in a solvent containing no free hydroxyl groups such as a hydrocarbon or an ether. The reduction step is suitably effected with a complex metal hydride, e.g. lithium-aluminium hydride or sodium-boron hydride in the presence of an ether or by reduction with an alkali metal and an aliphatic mono- or dihydric alcohol, e.g. ethanol, propanol or glycol. The quantity of reducing agent may be such that any keto group contained in R11 is reduced to a hydroxyl group and any esterified hydroxyl groups Y1 and/or Y2 are converted to free hydroxyl groups. If Y1 and/or Y2 are benzyl groups they may be subsequently converted to free hydroxyl groups by catalytic hydrogenation. In examples (1) 1-p-hydroxyphenyl-2-amino-propanol-(1) is treated with phenoxyacetic anhydride and the resulting 1-p-hydroxyphenyl - 2 - a - phenoxyacetamido - propanol-(1) is reduced with lithium aluminium hydride to 1 - p - hydroxyphenyl - 2 - b - phenoxyethyl - amino - propanol - (1); (2) p - hydroxy - a - amino-propiophenone is treated with phenoxyacetyl chloride and the resulting p-hydroxy-a -phenoxyacetamido-propiophenone is treated with lithium aluminium hydride to give the product of (1); (3) phenoxyacetic anhydride is used in place of phenoxyacetyl chloride in the process of (2) and (4) p-hydroxy-a -amino-propiophenone is treated with g -phenoxybutyryl chloride to give p-hydroxy-a -(g -phenoxybutyrylamido)-propiophenone which is reduced with lithium aluminium hydride to 1-(p-hydroxyphenyl)-2-(41 - phenoxybutylamino) - propanol - (1). Specifications 800,718, 832,286, 832,287 and 832,288 are referred to.