Patent GB-832287-A (GB)
Title: Improvements in or relating to processes for producing substituted alkylamines and acid-addition salts thereof
Filed: 1957-10-11
Abstract: Amines of the formula <FORM:0832287/IV (b)/1> or acid-addition salts thereof, wherein Y1 and Y2 are hydrogen, hydroxyl or etherified or esterified hydroxyl groups R1 is an alkylene or hydroxyalkylene group of 2-6 carbon atoms in which the hydroxyl group may not be attached to the carbon atom adjacent to the nitrogen atom and R2 is an alkylene group of 2-6 carbon atoms, are made by reaction of a compound of the formula <FORM:0832287/IV (b)/2> or an acid addition salt thereof, with a compound of the general formula <FORM:0832287/IV (b)/3> wherein R11 is an alkylene, hydroxyalkylene or keto-alkylene group of 2-6 carbon atoms corresponding to R1 and X is a halogen atom, reducing the keto group if any to a hydroxyl group and, if desired, prior to or after this reduction, converting the esterified or etherified groups Y1 and/or Y2, if any, into hydroxyl groups by hydrolysis or hydrogenation.  Suitably, X is a bromine or iodine atom; Y1 and/or Y2 represent a hydroxyl group, an etherified hydroxyl group (e.g. benzyloxy), or a hydroxyl group esterified, for example by an aliphatic carboxylic acid or benzoic acid, preferably in the para position; R2 is an ethylene, isopropylene or n-propylene group and R11NH is a group -CH(OH).R5NH or CO.R5NH, wherein R5 is an alkylene group of 1-5 carbon atoms.  The reaction is suitably effected using the freamine Y1.C6H4.R11.NH2 or its salt with a weak acid, e.g. the acetate, carbonate or propionate, or is effected in the presence of an acid-binding agent which may be a salt of an acid of low volatility, a tertiary amine, or an excess of the amine reactant.  The reaction may be carried out in a solvent, e.g. ethanol, methanol, propanol, dimethyl ether, diethyl ether, decahydro-naphthalene, ligroin, benzene or toluene or an excess of one of the reaction components may be used.  A reaction temperature of 50 DEG  to 200 DEG  C. for 6-48 hours is preferred.  Hydrolysis of an ester group Y1 and/or Y2 may be carried out with aqueous or alcoholic solutions of acids or bases; hydrogenolysis of etherified groups Y1 and/or Y2 is suitably carried out catalytically, whereby any keto group is also converted to a free hydroxy group.  Also if Y1 and/or Y2 are esterified groups and the molecule contains a keto group, they may be converted into free hydroxyl groups by reduction with a complex metal hydride having two different metal atoms to give simultaneous reduction of the keto group.  The compounds are used pharmaceutically.  In examples: (1) 2-phenoxyethyl bromide is reacted with 1-(41-hydroxyphenyl) - 2 - amino - propanol - (1) to give 1 - (41 - hydroxyphenyl) - 2 - (21 - phenoxyethylamino) - propanol - (1), isolated as the hydrochloride; (2) 1 - (41 - hydroxyphenyl) - 2-amino - propanol is treated with 1 - phenoxy-2 - bromo - propane to give 1 - (41 - hydroxyphenyl) - 2 - (11 - methyl - 21 - phenoxyethylamino) - propanol - (1) (hydrochloride) and (3) 1 - (41 - hydroxyphenyl) - 2 - amino - propanol is treated with 3-phenoxypropyl bromide to give 1 - (41 - hydroxyphenyl) - 2 - (31 - phenoxypropylamino) - propanol - (1) (hydrochloride).  1-Phenoxy-2-bromo-propane is made by prolonged reaction of phosphorus tribromide on 1-phenoxy propanol-(2). Specifications 800,718, 832,286, 832,288 and 832,289 are referred to.