反应详情

To Intermediate 80 (131.02 g, combination of two batches) under nitrogen in methanol (1000 mL) and dichloromethane (DCM) (1000 mL) was added sodium borohydride (29.4 g) slowly in portions over 10 min and the mixture stirred at room temperature under nitrogen. Temp rose from 19° C. to 23° C. Gas evolution still visible for 20-30 mins and temp rose over 40 mins to 26° C. Temp still going up after 1 hr20 min—now 26.2° C. After 2.5 hr water was added carefully and the mixture was partitioned between ethyl acetate and water (should have given the mixture more time to quench before extracting—gas evolution during extraction seen) and the aqueous layer extracted well with ethyl acetate. The combined organics were washed with water, brine, dried (MgSO4), filtered and evaporated. This gave the title compound, a white solid, 133.3 gm. LC/MS MH+ 339, 341, Rt 0.76 min (2 min run).

1. customrose from 19° C. to 23° C
2. customafter 1 hr20 min—now 26.2° C
3. customthe mixture was partitioned between ethyl acetate and water (
4. customto quench before extracting—gas evolution during extraction
5. extractionextracted well with ethyl acetate
6. washThe combined organics were washed with water, brine
7. dry with materialdried (MgSO4)
8. filtrationfiltered
9. customevaporated