Diethyl Ether → (2R)-1-[2-methyl-5-(trifluoromethyl)phenyl]propan-2-ol

Temperature

-105 °C

A solution of 2-bromo-1-methyl-4-(trifluoromethyl)benzene (4.78 g, 20 mmol) in 100 mL of anhydrous THF was cooled to −100° C. (liquid nitrogen/EtOH) under nitrogen. Then 1.4M solution of sec-BuLi in cyclohexane (15 mL, 21 mmol) was added dropwise at −100° C. to −90° C. The mixture was stirred at −100° C. to −90° 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 (silicagel, EtOAc/hexane 1:9, Rf=0.45 in EtOAc/hexane 3:7) to give (2R)-1-[2-methyl-5-(trifluoromethyl)phenyl]propan-2-ol (2.87 g, 66%) as white solid. 1H NMR (300 MHz, CDCl3): δ 7.42 (s, 1H), 7.39 (d, J=8.1 Hz, 1H), 7.27 (d, J=8.1 Hz, 1H), 4.06 (m, 1H), 2.81 (d, J=6.39 Hz, 2H), 2.39 (s, 3H), 1.43 (d, J=4.14 Hz, 1H), 1.29 (d, J=6.21 Hz, 3H).

1. stirringThe mixture was stirred at −100° C. to −90° C. for 2 h
2. customthe reaction was quenched with 20 mL of sat. aq. NH4Cl at −90° C
3. stirringThe mixture was stirred
4. temperaturewarmed to 0° C. overnight
5. additionThen 20 mL of water was added
6. extractionmixture was extracted with EtOAc (2×60 mL)
7. dry with materialthe extract was dried over Na2SO4
8. customevaporated
9. customto give crude oil, which
10. customwas purified by column (silicagel, EtOAc/hexane 1:9, Rf=0.45 in EtOAc/hexane 3:7)

ORD record

ord-df2017516cdb43eea7326e7e3c53d51c

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09249147B2