合成路线1

A new total synthesis of sertraline has been described: The reduction of N,N-dibenzyl-D-phenylglycine methyl ester (I) with LiAlH4 in THF gives alcohol (II), which is oxidized to aldehyde (III) with oxalyl chloride in dichloromethane. The condensation of (III) with the phosphorane (IV) in benzene yields the unsaturated ester (V), which is reduced with Mg in methanol affording the saturated methyl ester (VI). Reduction of (VI) with LiAlH4 in THF provides the corresponding butanol derivative (VII), which is oxidized to the aldehyde (VIII) with pyridinium dichromate (PDC) in dichloromethane. The Grignard reaction of (VIII) with 3,4-dichlorophenylmagnesium bromide (IX) in THF affords the secondary alcohol (X), which is cyclized by means of AlCl3 in dichloromethane yielding a mixture of the desired cis-isomer (XI) along with some trans-isomer separated by column chromatography. Debenzylation of (XI) by H2 over Pd(OH)2 in methanol, followed by protection with Boc2O yields the carbamate (XII), which is methylated with methyl iodide and NaH in THF to afford the protected intermediate (XIII). Finally, compound (XIII) is deprotected with TFA in dichloromethane.