N. S. Donskaya, O. A. Antonkina, E. Glukhan
Jul 1, 2004
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Journal
Pharmaceutical Chemistry Journal
Abstract
4-Chloro-N-(3-morpholinopropyl)benzamide (befol, I) is an original domestic antidepressant belonging to the class of type A reversible MAO inhibitors [1]. The commercial production of befol includes the following stages: (i) synthesis of 4-chlorobenzoic acid chloroanhydride (II) [2]; (ii) syntesis of 3-morpholinopropionitrile (III) [3 – 6]; (iii) catalytic reduction of compound III to N-(3-aminopropyl)morpholine (IV) by hydrogen (30 – 40 bar) at 100 – 150°C in an excess of ammonia [3]; and (iv) synthesis of befol via the reaction between compounds IV and II in pyridine. Disadvantages of the existing scheme are the use of highly toxic acrylonitrile in the stage of nitrile synthesis and the low efficiency of the stage of catalytic reduction of nitrile III. We believe that a more convenient and effective scheme is offered by befol (I) synthesis via the interaction of 4-chloro-N-(3-chloropropyl)benzamide (V) with morpholine (VI) in the presence of a hydrogen chloride acceptor. All reactants necessary for the synthesis of benzamide V can be obtained with high yields using standard methods.