反应详情

Powdered sodium borohydride (98%, 2.868 g, 75.5 mmol) was added to a solution of methanol (80 mL) and tetrahydrofuran (400 mL), and the mixture was stirred vigorously for 5 min. The product of Example 3, Step A (13.9 g, 75.5 mmol) was dissolved in tetrahydrofuran (400 mL) and the resulting solution was added dropwise to the sodium borohydride suspension at a constant rate of approximately 33 mL/min. The appearance of the reaction mixture changed from a light yellow slightly cloudy suspension to a clear red solution. Reaction progress was monitored by thin layer chromatography eluting with a 10% methanol: 40% dichloromethane: 50% toluene solvent. Upon reaction completion, acetic acid (3 mL) was added dropwise, and the reaction mixture was stirred for 5 min. Acetic acid (2 mL) and water (30 mL) were added, the reaction mixture was briefly stirred, and then ethyl acetate was added (500 mL). The reaction mixture was washed with 1 N aqueous sodium hydroxide solution (300 mL), dried over magnesium sulfate, filtered, and the solvent was removed under reduced pressure at 50° C. The resulting crude oil was dissolved in dichloromethane (50 mL) and the solution was eluted through a plug of silica gel (100 g) with ethyl acetate (3 L). The eluant was concentrated to a yellow-orange oil which slowly crystallized to provide 8.909 g (63.4%) of the title product as a pale yellow solid.

1. customReaction progress
2. washeluting with a 10% methanol
3. customUpon reaction completion, acetic acid (3 mL)
4. additionwas added dropwise
5. stirringthe reaction mixture was stirred for 5 min
6. stirringthe reaction mixture was briefly stirred
7. washThe reaction mixture was washed with 1 N aqueous sodium hydroxide solution (300 mL)
8. dry with materialdried over magnesium sulfate
9. filtrationfiltered
10. customthe solvent was removed under reduced pressure at 50° C
11. dissolutionThe resulting crude oil was dissolved in dichloromethane (50 mL)
12. washthe solution was eluted through a plug of silica gel (100 g) with ethyl acetate (3 L)
13. concentrationThe eluant was concentrated to a yellow-orange oil which
14. customslowly crystallized