Hydrochloric Acid → (3R)-3-[(1S)-1-(3,4-Dichlorophenyl)-3-(4-(2-methylsulfinylphenyl)-piperidino)propyl]-2-methyl-2,3-dihydroisoindol-1-one hydrochloride

Participants

Reaction Steps

A solution of (3S)-3-(3,4-dichlorophenyl)-3-[(1R)-2-methyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl]propionaldehyde (0.54 g) in methanol (10 mL) was treated with 4-(2-methylsulfinylphenyl)piperidine (0.61 g) and the pH was adjusted to 3 with acetic acid and triethylamine. After treating with sodium cyanoborohydride (189 g) the reaction mixture was stirred at ambient temperature for 16 hours, acidified with 10% hydrochloric acid, stirred for 15 minutes and then diluted with a saturated solution of sodium bicarbonate. Upon extraction with dichloromethane, the organic layer was dried and evaporated to obtain the crude product. This material was purified by chromatography, with 20:1 dichloromethane:methanol as the eluent to give the desired 3-[1-(3,4-dichlorophenyl)-3-(4-(2-methylsulfinylphenyl)piperidino)propyl]-2-methyl-2,3-dihydroisoindol-1-one (0.414 g). This material was transformed into the hydrochloride salt as follows. The material was dissolved in dichloromethane (2 mL) and treated with hydrochloric acid in ether (2 mL). The resulting solution was diluted with anhydrous ether (80 mL), stirred for 4 hours, and the resulting precipitate was collected to afford the title compound (0.35 g); mp 180°-188° C.; MS: m/z=555<M+1); NMR(CD3SOCD3): 2.0 (broad,2), 2.3 (broad,2), 2.7 (s,3), 3.1 (s,3), 3.6 (t,2, J=15), 3.76 (m,1), 4.9 (d,1, J=2.4), 6.8 (d,1, J=7.8), 7.0 (s,1), 7.3-7.98 (m,9). Analysis for C30H32C.HCl.H2O: Calculated: C, 59.07; H, 5.78; N, 4.59; Found: C, 59.06; H, 5.72; N, 4.45.

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