Ethyl Acetate → HCID 86685073, compound

Temperature

0 °C

To a solution of 1-bromo-2-iodo-4-methylbenzene (18.5 g, 62.3 mmol) in THF (50 mL) at 0° C. was slowly added i-PrMgCl (12 mL, 23.47 mmol). After stirring for 1 h at 0° C., the reaction temperature was cooled to −70° C. Then a solution of 1,3-difluoropropan-2-one (1.7 g, 18.05 mmol) in dry THF (5 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 2 N HCl 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 eluted with PE:EA (25:1) to give the desired product (2.5 g, yield 53%) as colorless oil. 1H NMR (300 MHz, CDCl3): δ 7.61 (d, J=1.8 Hz, 1H), 7.46 (d, J=8.1 Hz, 1H), 7.02-6.99 (m, 1H), 5.13-5.09 (m, 1H), 5.02-4.94 (m, 2H), 4.87-4.82 (m, 1H), 3.27 (bs, 1H), 2.33 (s, 3H) ppm.

1. customat 0° C.
2. temperaturethe reaction temperature was cooled to −70° 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. washeluted with PE

ORD record

ord-44e39a5d21b14377bb2773fc578240b4

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08853186B2