1,4-Dioxane → 3-(2-Bromo-acetyl)-6-fluoro-2-methyl-benzonitrile

Participants

Reaction Conditions

Reaction Steps

Degassed Reactant Sn reagent (200 ml, 591 mmol) was added to a stirred mixture of 3-Bromo-6-fluoro-2-methylbenzonitrile (115 g, 537 mmol) and PdCl2(PPh3)2 (18.86 g, 26.9 mmol) in dioxane (1149 ml) at RT, then degassed with N2 and the mixture was stirred at 100° C. for 22 hours. The reaction was cooled to 0° C. and THF (575 mL) and water (230 mL) were added followed by NBS (110 g, 618 mmol) added portionwise over 15 min. After 30 minutes, HPLC showed full consumption of the intermediate ketone. The solution was diluted with MTBE (1000 mL) and washed with 0.5% aqueous HBr (3×500 mL), then washed with water. The organic layers were dried over Na2SO4, filtered and concentrated. A precipitate generated. The solid was filtered and washed several times with hexanes to give the title product.

Provenance & Evidence