Ethyl Acetate → 2-(2-Bromo-4-methylphenyl)-1,3-difluoropropan-2-ol

Temperature

0 °C

To a solution of 2-bromo-1-iodo-4-methylbenzene (18.5 g, 62.3 mmol) in THF (25 mL) at 0° C. was slowly added i-PrMgCl (24 mL, 24 mmol). After being stirred for 1 h at 0° C., the reaction mixture was cooled to −78° C. Then a solution of 1,3-difluoropropan-2-one (0.85 g, 9.04 mmol) in dry THF (25 mL) was added. The mixture was stirred at −70° C. for 1 h, and then dry ice bath was removed. The solution was acidified with HCl (2 N) and extracted with EA (60 mL×2). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography over silica gel, eluting with PE:EA (5:1) to give 2-(2-bromo-4-methylphenyl)-1,3-difluoropropan-2-ol (1.3 g, yield 55%) as colorless oil. 1H NMR (400 MHz, DMSO-d6): δ 7.60 (d, 1 H), 7.46 (s, 1 H), 7.21 (d, 1 H), 6.21 (s, 1 H),4.97-4.94 (m, 1 H), 4.85-4.82 (m, 2 H), 4.74-4.71 (m, 1 H), 2.26 (s, 3 H) ppm.

1. customat 0° C.
2. temperaturethe reaction mixture was cooled to −78° C
3. stirringThe mixture was stirred at −70° C. for 1 h
4. customdry ice bath was removed
5. extractionextracted with EA (60 mL×2)
6. washThe combined organic layers were washed with brine
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customThe residue was purified by column chromatography over silica gel
11. washeluting with PE

ORD record

ord-c1e443674ae94ef8a9e133030f6cf473

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08546357B2