合成路线1

A new synthesis of [7-3H]-sertraline has been described: The optical resolution of 7-bromo-1-(methylamino)tetraline (I) with N-acetyl-D-phenylalanine gives the (R)-isomer (II), which is acylated with formic acid - acetic anhydride to the formamide (III). The oxidation of (III) with KMnO4 in acetone - water yields 6-bromo-4(R)-(methylamino)-1,2,3,4-tetrahydronaphthalen-1-one (IV), which, by a Grignard condensation with 3,4-dichlorophenylmagnesium bromide (V) in ether - toluene, affords 6-bromo-1(S)-(3,4-dichlorophenyl)-4(R)-(N-methylformamido)-1,2,3,4-tetrahydronaphthalen-1-ol (VI). The reduction of (VI) with triethylsilane tetrafluoroborate in dichloromethane gives 6-bromo-1(S)-(3,4-dichlorophenyl)-4(R)-(N-methylformamido)tetraline (VII), which is hydrolyzed with HCl in isopropanol to the corresponding methylamine (VIII). Oxidation of (VIII) with NaClO NaOCH3 in methanol - water yields the imine (IX), which is reduced with NaBH4 in THF - methanol to 6-bromo-1(S)-(3,4-dichlorophenyl)-4(S)-(methylamino)tetraline (X), along with starting (VIII). After separation by column chromatography, (X) is reduced with H2 over Pd/C or with T2 over Pd/C in THF containing triethylamine.