Water → (3-(2-(3-Chlorophenyl)ethyl)-2-pyridinyl)(1-methyl-4-piperidinyl)methanone hydrochloride

Participants

Reaction Conditions

Reaction Steps

To a solution of product of Step C above (118 g, 0.487 mole) in 1.2 L of dry tetrahydrofuran is added 395 mL (2.48 mole/liter, 0.585 mole, 1.2 eg.) of N-methyl-piperidyl magnesium chloride over about 15 minutes maintaining the temperature at 45° C.-50° C. by cooling with water as necessary. The reaction is maintained at 40° C. to 50° C. for about another 30 minutes. Completion of the reaction is determined by thin-layer chromatography. The reaction is quenched to pH below 2 with 2N hydrochloric acid and the resulting solution is stirred at about 25° C. for 1 hour. The bulk of the tetrahydrofuran is removed by distillation and the resulting solution is adjusted to pH 3.5 by the addition of aqueous sodium hydroxide. After cooling to 0° to 5° C., the crystalline hydrochloride salt product is filtered off, washed with ice cold water and dried to constant weight at 60° C. Yield: 168.2 g (HALC purity 94%), m.p. 183°-185° C., 89% of theory.

Provenance & Evidence