Diethyl Ether → HCID 86677135, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 1,2-difluoro-4,5-dimethoxybenzene (3.48 g, 20 mmol) in 10 mL of anhydrous THF was slowly added to a cooled at −78° C. solution of sec-BuLi in THF/cyclohexane (1.4M in cyclohexane, 15 mL, 21 mmol mixed with 80 mL of THF). The mixture was stirred at −70° C. for 10 min, then a solution of R-(+)-propylene oxide (1.51 g, 1.8 mL, 26 mmol) in 15 mL of THF was added dropwise at −100° C. to −90° C., 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 mixture was extracted with EtOAc (2×60 mL), the extract was dried over Na2SO4 and evaporated to give crude oil, which was purified by column (silica gel, EtOAc/hexane 1:9, Rf=0.29 in EtOAc/hexane 3:7) to give (2R)-1-(2,3-difluoro-5,6-dimethoxyphenyl)propan-2-ol (883 mg, 19%) as pale oil. 1H NMR (300 MHz, CDCl3): δ 6.65 (m, 1H), 4.06 (m, 1H), 3.83 (s, 3H), 3.82 (s, 3H), 2.87 (m, 2H), 2.05 (d, J=4.71 Hz, 1H), 1.25 (d, J=6.24 Hz, 3H).

Provenance & Evidence