GB728406A - Process for the preparation of 5-hydroxytryptamine and addition salts thereof - Google Patents

Abstract

5.-Hydroxytryptamine of the formula <FORM:0728406/IV (b)/1> or an addition salt thereof is prepared by debenzylating, by catalytic hydrogenation, a 5-benzyloxytryptamine or an addition salt thereof. The 5-benzyloxytryptamine is prepared from 5-benzyloxyindole of the formula <FORM:0728406/IV (b)/2> wherein X is a phenyl or substituted phenyl radical and Y is a phenyl or substituted phenyl, alkyl or cycloalkyl radical or hydrogen, by reaction with a Grignard reagent, reacting the resulting 5-benzyloxyindole magnesium halide with a haloacetonitrile to produce a 5-benzyloxy-3-indoleacetonitrile, and reducing the 5-benzyloxy-3-indoleacetonitrile to produce a 5-benzyloxytryptamine. The latter step may be carried out with lithium aluminium hydride, sodium and alcohol, or lithium borohydride, or by means of hydrogen in the presence of platinum catalyst. The 5-benzyloxytryptamine or its salt is debenzylated with hydrogen in the presence of a catalyst, preferably a 10 per cent palladium-charcoal catalyst, in the presence of a solvent such as an alkanol or lower ketone. The free 5-hydroxytryptamine base may be converted into an acid addition salt by adding a stoichiometric quantity of the acid to a solution of the base and adding a precipitating agent for the salt, e.g. acetone for precipitating the creatinine sulphate salt, ether for the sulphate, hydrochloride, acetate or citrate, and water for the picrate. The precipitation is usually conducted at the boiling point. In examples (1) 5-benzyloxyindole is added to a Grignard reagent prepared from magnesium and methyl iodide, followed by chloroacetonitrile, and the 5 - benzyloxy - 3 - indole - acetonitrile is reduced with lithium aluminium hydride to give 5-benzyloxytryptamine, which is then treated with hydrogen and palladium-charcoal catalyst in the presence of ethanol and the 5-hydroxytryptamine precipitated as the creatinine sulphate addition salt by means of sulphuric acid and creatinine sulphate solution; (2) 5-hydroxytryptamine is prepared by debenzylating 5-(p-methylbenzyloxy)-tryptamine by means of hydrogen as in (1); and in other examples, 5-hydroxytryptamine and its creatinine sulphate salt are similarly prepared from (3) 5-(p-benzylbenzyloxy) - tryptamine, (4) 5 - (p - methoxybenzyloxy) - tryptamine, (5) 5 - benzhydryloxytryptamine, (6) 5-(p-cyclopentylbenzyloxy)-tryptamine, (7) 5 - (p - iodobenzyloxy) - tryptamine, (8) 5 - (a - methylbenzyloxy) - tryptamine, and (9) 5 - (a - cyclohexylbenzyloxy)-tryptamine. The examples also specify a large number of alternative substituted 5-benzyloxyindoles within the general formula given above, as starting materials in the process.