Sodium borohydride → HCID 67159214, compound

Participants

Reaction Conditions

Reaction Steps

A solution of methyl (1RS,3RS)-3-(4-chloro-3-(trifluoromethyl)phenyl)-3-methyl-4-oxocyclohexane-carboxylate (1.348 g, 3.87 mmol) in ethanol (20 mL) was treated with sodium borohydride (0.292 g, 7.73 mmol) and stirred at 60° C. Additional sodium borohydride (100 mg) was added after 7 h and again after 22.75 h. After 28 h, the resulting mixture was concentrated under vacuum and the resulting residue was stirred with ethyl acetate and saturated aqueous sodium bicarbonate for 30 min. The aqueous and organic layers were separated and the aqueous phase was extracted with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated under vacuum to yield a residue. This residue was purified by column chromatography on silica gel, eluting with 30-70% ethyl acetate-hexanes, to provide (1RS,2RS,4RS)-2-(4-chloro-3-(trifluoromethyl)phenyl)-4-(hydroxymethyl)-2-methylcyclohexanol as a white glassy foam (967 mg, 78%). 1H NMR (500 MHz, CDCl3) δ 8.14 (d, J=2.2 Hz, 1 H), 7.82 (dd, J=8.5, 2.2 Hz, 1 H), 7.41 (d, J=8.8 Hz, 1 H), 3.76 (dd, J=12.1, 3.8 Hz, 1 H), 3.45 (ab portion of abx, 2 H), 2.37 (dt, J=14.3, 2.7 Hz, 1 H), 1.92 (br. s, 1 H), 1.82 (m, 1 H), 1.77 (m, 1 H), 1.58 (m, 3 H), 1.35 (s, 3 H), 1.18 (m, J=14.0, 12.4 Hz, 2H).

Provenance & Evidence