Boron trifluoride etherate → HCID 67158691, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 5-bromo-2-chloro-1-trifluoromethyl-benzene (1.09 mL, 7.34 mmol) in THF (20 mL) was stirred at −78° C. and treated with n-butyllithium (1.6 M in hexane, 4.59 mL, 7.34 mmol). The resulting solution was stirred at −78° C. for 30 min and then treated with boron trifluoride etherate (924 μL, 7.34 mmol). After stirring for an additional 10 min, a solution of (1RS,3RS,6SR)-3-(benzyloxy)-7-oxa-bicyclo[4.1.0]heptane (prepared according to the procedure of Chini et al., J. Org. Chem. 1990, 55, 4265; 1.00 g, 4.90 mmol) in THF (4.0 mL) was added over a 5 min period. Upon completion of addition, the mixture was stirred at −78° C. for 70 min and then poured into saturated aqueous ammonium chloride. This mixture was extracted three times with ethyl acetate, and the combined organic phases were dried over sodium sulfate and concentrated under vacuum to yield a residue. The residue was purified by column chromatography on silica gel, eluting with 20-60% ethyl acetate-hexanes, to provide (1SR,2RS,4RS)-4-(benzyloxy)-2-(4-chloro-3-(trifluoro-methyl)phenyl)cyclohexanol as a colorless gum (958 mg, 51%). 1H NMR (400 MHz, CDCl3) δ 1.40 (bd, J=3.6 Hz, 1 H) 1.50-1.64 (m, 2 H) 1.82-1.97 (m, 2 H) 2.05-2.12 (m, 1 H) 2.12-2.20 (m, 1 H) 2.95-3.05 (m, 1 H) 3.65-3.74 (m, 1 H) 3.74-3.80 (m, 1 H) 4.54 (ab, J=12.2 Hz, 2 H) 7.27-7.40 (m, 6 H) 7.45 (d, J=8.7 Hz, 1 H) 7.55 (d, J=2.0 Hz, 1 H).

Provenance & Evidence