Meptazinol hydrochloride, Wy-22811(free base), Meptid

盐酸美普他酚 美普他酚 Chemical Name: 1-Methyl-3-ethyl-3-(3-hydroxyphenyl)hexahydro-1H-azepine hydrochloride
CAS No. 59263-76-2, 54340-58-8 (free base)
项目整合开发状态: Launched-1983
项目研究机构: Wyeth Pharmaceuticals (Originator), Shire Pharmaceuticals (Licensee)
合成路线:By condensation of 2-(m-methoxyphenyl)butyronitrile (I) with ethyl 4-iodobutyrate (A) by means of NaNH2 in liquid NH3 to give ethyl 5-cyano-5-(m-methoxyphenyl)heptanoate (II),which is cyclized by hydrogenation with H2 over Raney-Ni in C6H12 to yield 6-ethyl-6-(m-methoxyphenyl)hexahydro-2H-azepin-2-one (III); this ketone is reduced with LiAlH4 in THF to 3-ethyl-3-(m-methoxyphenyl)hexahydro-1H-azepine (IV),which in turn,is reductively methylated with HCHO,H2 and Pd/C in ethanol to give 1-methyl-3-ethyl-3-(m-methoxyphenyl)hexahydro-1H-azepine (V),and finally demethylated by refluxing with 80% HBr to yield a racemic mixture of the final product.

合成路线:The optically active isomers are obtained as follows: the methoxyazepine (IV) is demethylated with HBr as before to give 3-ethyl-3-(m-hydroxyphenyl) hexahydro-1H-azepine (VI); this product,by reaction with D-(+)-tartaric acid and fractionated crystallization can be separated into its (+)-isomer (+)-(VI) and (-)-isomer (-)-(VI).Both isomers are finally reductively methylated with HCHO,H2 and Pd/C in ethanol.