Citric Acid → (S)-N-[2-(3,4-Dichlorophenyl)-4-[4-(2-oxopiperidino)-4-(pyrrolidin-1-ylcarbonyl) piperidino]butyl]-N-methylbenzamide citric acid salt

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Reaction Steps

(S)-N-[2-(3,4-Dichlorophenyl)-4-oxobutyl]-N-methylbenzamide (350 rag) in methanol (3 mL) was added to a solution of 4-(2-oxopiperidino)-4-(pyrrolidin-1-ylcarbonyl)piperidine (330 mg) and acetic acid (0.07 mL) in methanol (5 mL). After 10 minutes, sodium cyanoborohydride (100 mg) in methanol (2 mL) was added in a single portion. After being stirred for 3 hours, the reaction mixture was diluted with aqueous sodium bicarbonate, stirred for 30 minutes, and extracted with dichloromethane. The organic extracts were dried, evaporated, and chromatographed, with dichloromethane:methanol (95:5) as eluent. The resulting material (410 mg) was dissolved in methanol containing 1 equivalent of citric acid (128 mg), evaporated, suspended and pulverized in ether, evaporated, and placed under high vacuum to give the title compound as a white solid (540 mg); MS: m/z=613(M+1), 542[(M+1)-pyrrolidine]. Analysis for C33H42Cl2N4O3 ·1.40 H2O·0.65 (C2H5)2O·1.0 C6H8O7 : Calculated: C, 56.83; H, 6.80; N, 6.37; Found: C, 56.89; H, 6.74; N, 6.27.

Provenance & Evidence