2-(2-chloro-6-fluorophenyl)acetyl chloride

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 2 M solution of trimethylsilyl-diazomethane in hexane (6.54 ml, 13.07 mmol) cooled to 0° C. under argon was added dropwise a solution of 2-chloro-6-fluoro-phenylacetyl chloride (1.23 g, 5.94 mmol) in 24 ml of a mixture of THF and ACN (1:1). The mixture was stirred at 0° C. for 5 h. Then 48% aqueous hydrobromic acid (5.91 ml, 52.28 mmol) was added dropwise and the solution was stirred at room temperature overnight. Then 40 ml of water were added. The aqueous phase was extracted twice with EA, and the combined organic phases were washed with water, a saturated solution of sodium hydrogencarbonate and brine, dried over sodium sulfate, filtered and evaporated to dryness under reduced pressure. The residue was purified by chromatography on silica gel (cyclohexane/EA, 100:0, then 95:5) to give 1.20 g of the title compound as a white powder having a melting point of 47° C. the solution was stirred at room temperature overnight The aqueous phase was extracted twice with EA the combined organic phases were washed with water a saturated solution of sodium hydrogencarbonate and brine, dried over sodium sulfate filtered evaporated to dryness under reduced pressure The residue was purified by chromatography on silica gel (cyclohexane/EA, 100:0