合成路线1

This compound has been obtained by several related ways. 1.- The condensation of 1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5- carbonitrile (I) with 3-chloropropyl tosylate (II) by means of LDA in THF gives 1-(4-fluorophenyl)-1-(3-tosyloxypropyl)-1,3-dihydroisobenzofuran-5-carbonitrile (III), which is then condensed with dimethylamine in hot DMF to yield the target citalopram. 2.- The condensation of 1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5- carbonitrile (I) with 3-chloropropyl mesylate (IV) by means of LDA in THF gives 1-(4-fluorophenyl)-1-(3-mesyloxypropyl)-1,3-dihydroisobenzofuran-5- carbonitrile (V), which is then condensed with sodium azide in hot DMF to yield the corresponding azido derivative (VI). The reduction of (VI) with H2 over Pd/C in ethanol affords the 3-aminopropyl derivative (VII), which is finally reductively methylated with formaldehyde and NaBH3CN in methanol to provide the target citalopram. 3.- The reaction of mesylate (V) with methylamine in THF gives the corresponding methylaminopropyl derivative (VIII), which is finally methylated by means of HCHO in refluxing HCOOH to yield the target citalopram. 4.- The direct condensation of mesylate (V) with dimethylamine in hot ethanol/THF also gives the target citalopram.