Benzyl mercaptan → HCID 25130204, compound

Temperature

0 °C

A solution of n-BuLi (2.5M in hexanes, 10 mL) was added slowly to a solution of benzyl mercaptan (3.6 mL, 40 mmol) in THF (40 mL) at 0° C. The resulting pale-yellow solution was stirred at 0° C. for 10 min prior to the introduction of (4R)-4-benzyl-3-({(1R,2R)-2-[(benzyloxy)methyl]-4,4-difluorocyclohexyl}carbonyl)-1,3-oxazolidin-2-one (8.52 g, 19.2 mmol) as a solution in THF (30 mL). After 10 min, a solution of LiAlH4 (1.0 M in THF, 22 mL) was slowly added to the reaction mixture with continued stirring at 0° C. for 45 min. Ice water was then slowly added to destroy excess hydride followed by 6M HCl (20 mL) to pH 1. The mixture was extracted with two portions of ethyl acetate and the combined organics were washed with saturated aqueous NaCl and dried over Na2SO4. Concentration in vacuo and flash chromatography of the residue on silica gel eluting with 45/55 ethyl acetate/hexanes afforded {(1R,2R)-2-[(benzyloxy)methyl]-4,4-difluorocyclohexyl}methanol as a thick, colorless syrup. 1H NMR (500 MHz, d6-acetone) δ 7.36 (4H, m), 7.34-7.28 (1H, m), 4.56-4.49 (2H, m), 3.67-3.53 (5H, m), 2.20-2.12 (1H, m), 2.09-2.02 (1H, m), 1.91-1.71 (4H, m), 1.58-1.50 (2H, m).

1. waitAfter 10 min
2. stirringwith continued stirring at 0° C. for 45 min
3. customto destroy excess hydride
4. extractionThe mixture was extracted with two portions of ethyl acetate
5. washthe combined organics were washed with saturated aqueous NaCl
6. dry with materialdried over Na2SO4
7. concentrationConcentration in vacuo and flash chromatography of the residue on silica gel eluting with 45/55 ethyl acetate/hexanes

ORD record

ord-efdf53af509f429b9226d0da34f40498

Source dataset

uspto-grants-2011_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07928091B2