Synthesis
A tetrahydrofuran solution of 3.00 M methylmagnesium chloride (125 mL, 0.38 mol) was added slowly and dropwise to a tetrahydrofuran (500 mL) solution of 4-bromo-3-fluoro-N-methoxy-N-methylbenzamide (58.5 g, 0.223 mol) at 0 °C. The reaction mixture was stirred continuously at 0 °C for 1 hour. Upon completion of the reaction, the reaction was quenched with pre-cooled saturated ammonium chloride solution (150 mL). The organic layer was separated and the remaining aqueous phase was extracted with ethyl acetate (3 x 50 mL). All organic phases were combined, washed with saturated brine, dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to afford the crude product 3-fluoro-4-bromoacetophenone (48.4 g, 99% yield), which could be used in the subsequent reaction without further purification.
References
[1] Patent: US2008/39457, 2008, A1. Location in patent: Page/Page column 41
[2] Patent: WO2008/64157, 2008, A1. Location in patent: Page/Page column 42-43
[3] Patent: US2009/291956, 2009, A1. Location in patent: Page/Page column 19
[4] Patent: US2011/212967, 2011, A1. Location in patent: Page/Page column 8
[5] Patent: WO2012/48421, 2012, A1. Location in patent: Page/Page column 24
