Patent GB-354226-A (GB)
Title: A process for preparing ?- and ?-hydroxy-phenyl-n-methyl-amino-ethanol-1
Filed: 1930-04-25
Abstract: m- and p-Hydroxyphenyl-N-methylamino-ethanol-1 are prepared by the catalytic hydrogenation in solution of m- and p-hydroxy-o -methylamino-acetophenone (see Specification 297,756, [Class 2 (iii), Dyes &c.]), or of their derivatives in which the hydrogen atom of the hydroxyl group is replaced by a hydrocarbon radicle or an acyl group. When using say the benzyloxy derivative, the benzyl group is split off during the hydrogenation, but in the case of acyloxy derivatives it is necessary to split off the acyl group by saponification.  The starting material may be in the form of the free base or of an optically-inactive salt thereof, and the hydrogen may react at ordinary or increased pressure.  The catalysts mentioned are palladium or other metals of the platinum group, platinum oxide and nickel, advantageously in a colloidal state and deposited on such carriers as carbon, barium sulphate and kieselguhr.  The solvents are of a non-alkaline nature, e.g. water, methyl or ethyl alcohol. Examples are given of the hydrogenation of (1) p-hydroxy-o -methylamino-acetophenone hydrochloride in aqueous or methanol solution using palladium-barium sulphate as catalyst to give p-hydroxyphenyl-N-methylamino-ethanol-1; (2) p-benzyloxy-o -methylamino-acetophenone in ethanol solution using a platinum catalyst; the benzyl group is eliminated as toluene simultaneously with the reduction of the keto group and p-hydroxyphenyl-N-methylamino-ethanol-1 is obtained; (3) m-hydroxy-o -methylamino-acetophenone hydrochloride in aqueous solution using nickel as catalyst to produce m-hydroxyphenyl-N-methylamino-ethanol-1; (4) m-benzoyloxy-o -methylamino-acetophenone hydrochloride in ethyl alcohol using nickel, and the benzoyl group then split off from the product by heating with hydrochloric acid to give m-hydroxyphenyl-N-methylamino-ethanol-1.ALSO:m- and p-Hydroxyphenyl-N-methylamino-ethanol-1 are prepared by the catalytic hydrogenation in solution of m- and p-hydroxy-o -methylaminoacetophenone (see Specification 297,756, [Class 2 (iii), Dyes &c.],) or of their derivatives in which the hydrogen atom of the hydroxyl group is replaced by a hydrocarbon radicle or an acyl group. When using say the benzyloxy derivative, the benzyl group is split off during the hydrogenation, but in the case of acyloxy derivatives it is necessary to split off the acyl group by saponification.  The starting material may be in the form of the free base or of an optically-inactive salt thereof, and the hydrogen may react at ordinary or increased pressure.  The catalysts mentioned are palladium or other metals of the platinum group, platinum oxide and nickel, advantageously in a colloidal form and deposited on such carriers as carbon, barium sulphate, and kieselguhr.  The solvents are of a non-alkaline nature, e.g. water, methyl or ethyl alcohol. The products possess therapeutic properties.  Examples are given of the hydrogenation of (1) p-hydroxy-o -methylamino-acetophenone hydrochloride in aqueous or methanol solution using palladium-barium sulphate as catalyst to give p-hydroxyphenyl-N-methylamino-ethanol-1; (2) p-benzyloxy-o -methylamino-acetophenone in ethanol solution using a platinum catalyst; the benzyl group is eliminated as toluene simultaneously with the reduction of the keto group and p-hydroxyphenyl-N-methylamino-ethanol-1 is obtained; (3) m-hydroxy - o  - methylamino - acetophenone hydrochloride in aqueous solution using nickel as catalyst to produce m-hydroxyphenyl-N-methylamino-ethanol-1; (4) m-benzoyloxy-o -methylamino-acetophenone hydrochloride in ethyl alcohol using nickel, and the benzoyl group then split off from the product by heating with hydrochloric acid to give m-hydroxyphenyl-N-methylamino-ethanol-1.  p-Benzyloxy-o -methylamino-acetophenone is obtained by treating p-oxyacetophenone with benzyl chloride in alkaline alcoholic solution, reacting with bromine on the product in benzene solution and treating the resulting p-benzyloxy-o -bromacetophenone with methylamine.  m-Benzoyloxy-o -methylaminoacetophenone is prepared by benzoylating m-oxyacetophenone, brominating the product and treating the m-benzoyloxy-o -bromacetophenone so formed with methylamine.