反应详情

温度

25 °C

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.

1. temperaturemaintaining the temperature at 45° C.-50° C.
2. temperatureThe reaction is maintained at 40° C. to 50° C. for about another 30 minutes
3. customThe reaction is quenched to pH below 2 with 2N hydrochloric acid
4. customThe bulk of the tetrahydrofuran is removed by distillation
5. additionthe resulting solution is adjusted to pH 3.5 by the addition of aqueous sodium hydroxide
6. temperatureAfter cooling to 0° to 5° C.
7. filtrationthe crystalline hydrochloride salt product is filtered off
8. washwashed with ice cold water
9. customdried to constant weight at 60° C