Diethyl Ether → (2R)-1-(2,5-difluorophenyl)propan-2-ol

Participants

Reaction Conditions

Reaction Steps

A solution of 2-bromo-1,4-difluorobenzene (3.85 g, 20.0 mmol) in anhydrous THF (100 mL) was stirred to −100° C. (liq. nitrogen/ethanol) under argon gas. Then, 1.6 M solution of sec-BuLi in cyclohexane (14.3 mL, 21.0 mmol) was added dropwise at −100° C.˜−90° C. for 10 min, then a solution of R-(+)-propylene (1.14 g, 1.4 mL, 26.0 mmol) in anhydrous THF (15 mL) was added dropwise at −100° C.˜−90° C. for 2 h, then the mixture was cooled to −105° C. and a 46.5% solution of BF3 in diethyl ether (4.18 mL, 30 mmol) was added dropwise. The mixture was stirred at −100° C. to −90° C. for 2 h, then the reaction was quenched with 20 mL of sat. aq. NH4Cl at −90° C. The mixture was stirred and warmed to 0° C. overnight. Then, 20 mL of water was added and extracted with EtOAc (2×60 mL), dried over anhydrous MgSO4, evaporated to give crude oil, which was purified by column chromatograpy (silicagel, EtOAc/hexane=1:9, v/v) to give (R)-1-(2,5-difluorophenyl)propan-2-ol (2.15 g, 62.5%). 1H NMR (CDCl3, 500 MHz) δ 6.98 (m, 2H), 6.88 (m, 1H), 4.10 (m, 1H), 4.03 (bs, OH), 2.79 (m, 1H), 2.71 (m, 1H), 1.23 (s, 3H).

Provenance & Evidence