ES316093A1 - Procedure for the manufacture of l - (-) -alfa methyl - beta- (3, 4-dihydroxypenyl) -alanin. (Machine-translation by Google Translate, not legally binding) - Google Patents

Abstract

L - ( - ) - [alpha] - Methyl - # - (3,4 - dihydroxyphenyl)-alanine is prepared by reacting 3,4- dimethoxyphenylacetone, or the bisulphite adduct thereof with an alkali metal cyanide and benzylamine, the [alpha]-benzylamino-[alpha]-(3,4-dimethoxybenzyl)-propionitrile obtained being resolved by using mol. d-(+)-camphor-sulphonic acid per mol. of racemate, the resolution being carried out in aqueous suspension in the presence of an organic solvent which is immiscible with water and with ice-cooling or at a temperature of 10-15 C., the precipitated camphor-sulphonic acid salt of the L-(+)- benzylaminonitrile being separated and converted into the free L-(+)-benzylaminonitrile, this conversion being carried out with cooling in an aqueous suspension in the presence of a waterimmiscible solvent, and the D-isomer remaining in the mother liquor being racemized in an alkaline medium to give the D,L-benzylaminonitrile which can be returned to the resolution step, the L (+) - [alpha] - benzylamino - [alpha] - (3,4 - dimethoxybenzyl) - propionitrile obtained then being converted into L-( - )-[alpha]-methyl-#-(3,4- dihydroxyphenyl)-alanine by first partially hydrolysing it with concentrated sulphuric acid to give an amide of formula followed, in any order, by debenzylation by catalytic hydrogenation, demethylation by hydrolysis, removal of the sulphonic acid group by hydrolysis and conversion of the amide group into a free carboxylic acid group by hydrolysis.L - (-) - a - Methyl - b - (3,4 - dihydroxyphenyl)-alanine is prepared by reacting 3,4-dimethoxyphenylacetone, or the bisulphite adduct thereof with an alkali metal cyanide and benzylamine, the a-benzylamino-a-(3,4-dimethoxybenzyl) -propionitrile obtained being resolved by using 1/2 mol. d-(+)-camphor-sulphonic acid per mol. of racemate, the resolution being carried out in aqueous suspension in the presence of an organic solvent which is immiscible with water and with ice-cooling or at a temperature of 10-15 DEG C., the precipitated camphor-sulphonic acid salt of the L-(+)-benzylaminonitrile being separated and converted into the free L-(+)-benzylaminonitrile, this conversion being carried out with cooling in an aqueous suspension in the presence of a water-immiscible solvent, and the D-isomer remaining in the mother liquor being racemized in an alkaline medium to give the D,L-benzylaminonitrile which can be returned to the resolution step, the L - (+) - a - benzylamino - a - (3,4 - dimethoxybenzyl) - propionitrile obtained then being converted into L-(-)-a-methyl-b-(3,4 -dihydroxyphenyl)-alanine by first partially hydrolysing it with concentrated sulphuric acid to give an amide of formula <FORM:1050838/C2/1> followed, in any order, by debenzylation by catalytic hydrogenation, demethylation by hydrolysis, removal of the sulphonic acid group by hydrolysis and conversion of the amide group into a free carboxylic acid group by hydrolysis.