Acetonitrile → 3-(4-Chloro-2-fluorophenyl)-3-oxopropanenitrile

温度

-78 °C

A 1.6 M hexane solution of n-butyllithium (39.8 mL, 63.6 mmol) was added to a solution of diisopropylamine (9.45 mL, 66.3 mmol) in THF (100 mL) at −78° C. over 10 min. The resultant solution was stirred at 0° C. for 30 min and cooled to −78° C. Acetonitrile (3.32 mL, 63.6 mmol) dropwise. The mixture was stirred at −78° C. for 30 min and then added a solution of 4-chloro-2-fluorobenzoate (5.00 g, 26.5 mmol) in THF (5 mL) at −78° C. dropwise. After stirring for 1 h at −78° C., the reaction mixture was quenched with brine (20 mL), warmed to room temperature and adjusted to pH 1-2 with 1N aqueous HCl. Following addition of ethyl acetate (400 mL), the mixture was washed with water (40 mL), brine (40 mL), dried (MgSO4) and concentrated to provide 3-(4-chloro-2-fluorophenyl)-3-oxopropanenitrile as tan solid (5.10 g, 97%). MS (ES+) m/z: 198 (M+H).

1. stirringAfter stirring for 1 h at −78° C.
2. customthe reaction mixture was quenched with brine (20 mL)
3. temperaturewarmed to room temperature
4. additionaddition of ethyl acetate (400 mL)
5. washthe mixture was washed with water (40 mL), brine (40 mL)
6. dry with materialdried (MgSO4)
7. concentrationconcentrated

ORDレコード

ord-28419f3597464cb7b8b27c0509d7d643

出典データセット

uspto-grants-2011_10

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08034940B2