反应详情

温度

0 °C

Solid NaOMe (6134 g) was added to a 0° C. solution of the chloroketone 2 (7062 g) in 49 L of methanol (MeOH) in portions over 2 h while maintaining the temperature at <20° C. The slurry was aged at room temperature for 1 h, at which time cyclization was determined to be complete by HPLC. The mixture was cooled to 0° C., and 2N HCl (49 L) was added while maintaining the temperature at <20° C. The slurry was cooled to 5-10° C., filtered, and washed first with cold 1:1 MeOH/water (5 L), and then with water (16 L). The wet filter cake was slurry washed with isopropyl alcohol (IPA) (18 L), and then was finally washed with heptane. The filter cake was then dried under a fast stream of nitrogen. Ketone 3 was isolated as a white solid.

1. temperaturewhile maintaining the temperature at <20° C
2. temperaturewhile maintaining the temperature at <20° C
3. temperatureThe slurry was cooled to 5-10° C.
4. filtrationfiltered
5. washwashed first with cold 1:1 MeOH/water (5 L)
6. washwashed with isopropyl alcohol (IPA) (18 L)
7. washwas finally washed with heptane
8. customThe filter cake was then dried under a fast stream of nitrogen