反应详情

温度

12.5 °C

A solution of the ketone, Compound 4, (512.2 g, 1.57 mol) in methanol (4.0 L) was split equally into two flasks. To each half of the ice-cold solution was added sodium borohydride (33.0 g, 0.87 mol) in batches (˜30 min). After the addition, the reaction solution was stirred at 0° C. (internal temperature 10-15° C.) for 50 min before it was quenched slowly with water (˜500 mL). The reaction mixture was then concentrated in vacuo to remove most of the organic solvent. The residue obtained from the two batches were combined, extracted with dichloromethane (2×), dried over sodium sulfate and concentrated in vacuo. The alcohol, Compound 5, was obtained as a yellow oil (510.4 g, quantitative), and was used in the next step without further purification: 1H NMR (500 MHz, CDCl3) δ 7.84-7.80 (m, 4H), 7.47-7.44 (m, 3H), 7.27-7.24 (m, 1H), 6.92-6.83 (m, 3H), 4.92 (dd, J=10.0, 4.0 Hz, 1H), 4.14 (br s, 1H), 3.81 (s, 3H), 3.74 (d, J=13.0 Hz, 1H), 3.53 (d, J=13.0 Hz, 1H), 2.68-2.60 (m, 2H), 2.36 (s, 3H); ESI MS m/z 322 [M+H]+.

1. additionAfter the addition
2. customwas quenched slowly with water (˜500 mL)
3. concentrationThe reaction mixture was then concentrated in vacuo
4. customto remove most of the organic solvent
5. customThe residue obtained from the two batches
6. extractionextracted with dichloromethane (2×)
7. dry with materialdried over sodium sulfate
8. concentrationconcentrated in vacuo