3-Chloropropionyl chloride → HCID 86721088, compound

Participants

Reaction Steps

In a flame-dried 3-neck flask, 2-bromo-4-chloro-1-fluorobenzene (2.0 g, 9.55 mmol) was dissolved in THF (anhydrous) (28.9 mL) under argon. Isopropylmagnesium chloride (2 M in THF) (5.01 mL, 10.03 mmol) was added, and the reaction was stirred at rt. To this solution was added zinc chloride (0.5 M in THF) (20.44 mL, 10.22 mmol) and the mixture was stirred at ambient temperature for 40 min. To the reaction was then added Pd(PPh3)4 (0.276 g, 0.239 mmol), and the mixture was cooled to 0° C. A solution of 3-chloropropanoyl chloride (0.981 mL, 10.22 mmol) in THF (2.89 mL) was added, and the reaction was stirred for 2 h at 0° C. The reaction mixture was then quenched with 3 N HCl, diluted with water, and extracted with Et2O (3×). The combined organics were dried (MgSO4), filtered and evaporated to yield a grainy yellow liquid, which was purified using silica gel chromatography to obtain a colorless oil, 3-chloro-1-(5-chloro-2-fluorophenyl)propan-1-one (0.405 g, 19%). MS (ESI) m/z: 221.0 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 7.88 (dd, J=6.3, 2.8 Hz, 1H), 7.51 (ddd, J=8.8, 4.3, 2.8 Hz, 1H), 7.13 (dd, J=10.2, 8.7 Hz, 1H), 3.94-3.88 (m, 2H), 3.46 (td, J=6.6, 3.2 Hz, 2H) ppm.

Provenance & Evidence