Ethyl Acetate → HCID 89924313, compound

Temperature

-78 °C

Potassium hydroxide (40 g, 714 mmol) was dissolved in water (100 mL) and acetonitrile (100 mL). The reaction mixture was cooled to −78° C. 1-(5-Fluoro-2-hydroxyphenyl)ethan-1-one (5 g, 32.44 mmol) was added to the reaction mixture and stirred for 5 minutes at −78° C. Diethyl[bromo(difluoro)methyl]phosphonate (11.5 mL, 64.88 mmol) was added dropwise to the mixture. The reaction mixture was stirred at −78° C. for 30 minutes, then warmed to room temperature over 1.5 h. The reaction mixture was diluted using EtOAc (2×100 mL). The mixture was washed with brine (50 mL). The organic phase was dried over sodium sulfate and concentrated in vacuo. The crude orange oil was purified by chromatography on silica (Biotage, 100 g cartridge), eluting with 0 to 40% ethyl acetate in heptanes, to afford the title compound (4.86 g, 74%) as a clear oil. δH (500 MHz, CDCl3) 7.47 (ddd, J 0.5, 3.0, 8.5 Hz, 1H), 7.24-7.14 (m, 2H), 6.55 (t, J 73.3 Hz, 1H), 2.62 (s, 3H). Method B HPLC-MS: RT 1.84 minutes, no mass ion observed.

1. stirringThe reaction mixture was stirred at −78° C. for 30 minutes
2. temperaturewarmed to room temperature over 1.5 h
3. additionThe reaction mixture was diluted
4. washThe mixture was washed with brine (50 mL)
5. dry with materialThe organic phase was dried over sodium sulfate
6. concentrationconcentrated in vacuo
7. customThe crude orange oil was purified by chromatography on silica (Biotage, 100 g cartridge)
8. washeluting with 0 to 40% ethyl acetate in heptanes

ORD record

ord-3f1ef8c3276549b6a041fd0b036d526d

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09309243B2