反应详情

Powdered 98% sodium borohydride (2.868 g, 75.5 mmole) was added to solution of methanol (80 mL) and tetrahydrofuran (400 mL), and the mixture was stirred vigorously for 5 minutes. The product of Step A (13.9 g, 75.5 mmole) 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/minute. 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 minutes. 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 1N 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. 1H NMR (CDCl3) δ 9.12 (s, 1H), 8.76 (s, 2H), 8.10 (d, 1H), 7.42 (t, 1H), 6.64 (t, 1H), 6.42 (d, 1H), 4.99 (br s, NH), 4.61 (d, 2H).

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 minutes
6. stirringthe reaction mixture was briefly stirred
7. washThe reaction mixture was washed with 1N 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