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

HRID 1090859Notes

Reaction equation

HRID 1090859 reaction equation
CN[C@@H]1C2C=CC=CC=2[C@H](C2C=CC(Cl)=C([Cl:19])C=2)CC1.[CH3:21][NH:22][CH:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:26]([C:33]2[CH:38]=[CH:37][C:36]([Cl:39])=[C:35]([Cl:40])[CH:34]=2)[CH2:25][CH2:24]1>O1CCCC1>[ClH:19].[CH3:21][NH:22][C@H:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[C@@H:26]([C:33]2[CH:38]=[CH:37][C:36]([Cl:39])=[C:35]([Cl:40])[CH:34]=2)[CH2:25][CH2:24]1

Participants

4

Reactant 2

HCID 52034-(3,4-Dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-naphthalenamineHCID 68617Sertraline

Product 1

HCID 13408688Sertraline hydrochloride, cis-(-)-

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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.

Sources & evidence

ORD record
ord-371e46d0954f4b36b259b806724c9643
Source dataset
uspto-grants-1992_01
Patent number
US05082970

Reaction notes

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