Synthesis of α-(3, 5-Dimethoxyphenyl)-β-monomethylaminoethanol, an Uterus Contraction Agent

Abstract

3, 5-Dimethoxyphenacyl halide (IX), an important intermediate for the preparation of α-(3, 5-dimethoxyphenyl)-β-monomethylaminoethanol (DMAE), can be obtained by the application of diazomethane to 3, 5-dimethoxybenzoyl chloride (VI) and subsequent decomposition of the diazoketone compound (VII) so formed with mineral acid, or the application of dimethylcadmium or acylmalonic ester to (VI) and bromination of the methyl ketone compound thereby formed. (IX) is derived to the amino ketone compound (XII) by the application of methylbenzylamine, its Meerwein reduction to the amino alcohol compound (XIII), and finally by debenzylation with palladium to DMAE. Application of dimethylamine to (IX) and reduction with nickel affords methyl-DMAE. The uterus contracting action of DMAE and methyl-DMAE on excised rabbit uterus by the Magnus method and their toxicity to mice are listed in Table I. DMAE is approximately the same as 6-allyl-2-methoxyphenyl diethylaminoethyl ether (AMAE) but the potency of methyl-DMAE was very slight.