PROCESS FOR THE PRODUCTION OF PHENYL-ALKYL-ETHYL-SALICIL-AMIDE

摘要

There are disclosed a process for producing (-)-5-{(R)-1-hydroxy-2-[(R)-1-methyl-3-phenylpropyl]aminoethyl} salicylamide and its acid addition salts in high yields which does not require chromatography, and important intermediates in this process. …The process is stereoselective for the desired (R,R) amine; a preferred embodiment includes the steps of (1) reaction of an N-[(R)-protected]-(R)-1-methyl-3-phenylpropylamine with a 4-O-protected 2-bromo-3-carbamoylacetophenone to produce the corresponding R,R-glycylbenzamide, (2) reduction to produce a mixture of S,R,R;R,R,R-hydroxybenzamides, (3) removal of the protecting groups, (4) resolution of the deprotected product and, if desired, conversion to the free R,R -amine or to another salt. …In this process, the selection of particular N-protecting groups has a very favourable effect, especialy in steps (2) and (3).