Hydrochloric Acid → (4-Chloro-8-fluoroquinazolin-2-yl)(4-fluorophenyl)methanone

Participants

Reaction Conditions

Reaction Steps

To a solution of ethyl 4-chloro-8-fluoroquinazoline-2-carboxylate (360 mg, 1.42 mmol) in THF (20 mL) at −40° C. was added 1M 4-fluorophenylmagnesium bromide/THF (1.7 mL, 1.7 mmol) and the mixture was stirred at −40° C. for 3 h. After this time, and additional portion of 1M 4-fluorophenylmagnesium bromide/THF (0.3 mL, 0.3 mmol) was added and the mixture was stirred at −40° C. for 2 h. To the mixture was added 0.5N HCl to give pH ˜2, and then saturated aq NaCl (50 mL) was added, and the mixture was extracted with EtOAc (3×50 mL). The combined organic layers were washed with brine (80 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure to afford (4-chloro-8-fluoroquinazolin-2-yl)(4-fluorophenyl)methanone (0.4 g, 93%). 1H NMR (300 MHz, DMSO-d6) δ 7.04-7.25 (m, 1 H), 7.31-7.58 (m, 2 H), 7.70-8.36 (m, 4 H); LC-MS (ESI) m/z 305 (M+H)+, 327 (M+Na)+.

Provenance & Evidence