Sodium borohydride → HCID 86713713, compound

Temperature

-78 °C

Compound C4 (3.00 g, 13.0 mmol) was dissolved in methanol (100 mL) and cooled to −78° C. Sodium borohydride (1.48 g, 39.1 mmol) was added portion-wise over 10 minutes, and the mixture was stirred at −78° C. for an additional 30 minutes before being allowed to warm to room temperature and stir for 1 hour. The reaction was quenched with saturated aqueous sodium bicarbonate solution (100 mL) and extracted with dichloromethane (2×150 mL). The organic layers were combined, washed with saturated aqueous sodium chloride solution (100 mL), dried over magnesium sulfate, filtered and concentrated under reduced pressure. Two purifications via silica gel chromatography [Gradients: 1) 0% to 50% ethyl acetate in heptane; 2) 0% to 50% dichloromethane in heptane] provided the title compound as a colorless oil. The product was tentatively assigned cis stereochemistry on the basis of NOE studies. Yield: 650 mg, 2.80 mmol, 22%. 1H NMR (400 MHz, CDCl3) δ 7.60 (br dd, J=7.8, 1.2 Hz, 1H), 7.47 (br ddd, J=8.2, 7.8, 1.2 Hz, 1H), 7.04 (br dd, J=7.6, 7.6 Hz, 1H), 6.87 (br d, J=8.4 Hz, 1H), 4.86-4.91 (m, 1H), 4.45-4.53 (m, 1H), 2.75 (d, J=9.2 Hz, 1H), 2.27-2.36 (m, 1H), 2.02-2.22 (m, 3H).

1. temperatureto warm to room temperature
2. stirringstir for 1 hour
3. customThe reaction was quenched with saturated aqueous sodium bicarbonate solution (100 mL)
4. extractionextracted with dichloromethane (2×150 mL)
5. washwashed with saturated aqueous sodium chloride solution (100 mL)
6. dry with materialdried over magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure

ORD record

ord-5851dacc8831460681d6d48e97db0820

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09193726B2