4-(3,4-Dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-naphthalenamine → Sertraline hydrochloride, cis-(-)-

As previously indicated, the 2:1 (by weight) cis/trans-mixture of racemic N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro- 1-naphthaleneamine isomers afforded as a final product of the process of this invention is valuable as an intermediate product that leads to the antidepressant agent known as sertraline or cis-(1S)(4S)-N-methyl-1,2,3,4-tetrahydro-1-naphthaleneamine. More specifically, when the aforesaid 2:1 (by weight) resultant cis/trans-mixture of racemic N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthaleneamine bases is first converted to the corresponding hydrochloride salts in an ethereal solvent system such as pure tetrahydrofuran, the pure crystalline racemic cis-amine salt exclusively separates from solution as a crystalline precipitate to afford pure racemic cis-N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthaleneamine hydrochloride, which is then recovered and converted back to the pure racemic cis-amine free base compound and subsequently resolved in a classical manner using the methods described by W. M. Welch, Jr. et al. in the aforesaid prior art to ultimately yield the desired pure cis-(1S)(4S)-N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthaleneamine (sertraline) as the hydrochloride salt. The corresponding 2:1 (by weight) cis/trans-mixture of chiral N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthaleneamine isomeric bases afforded as a final product of the process of this invention is similarly processed as an intermediate that leads to sertraline, except that the resolution step is not required since the desired pure chiral cis-(1S)(4S)-amine compound (sertraline) is obtained directly after isolation of the crystalline hydrochloride salt.