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0 °C

To a solution of 4-bromo-3-fluoro-N-methoxy-N-methylbenzamide (Step 1, 58.5 g, 223 mmol) in tetrahydrofuran (500 mL) was added 3M of methylmagnesium chloride in THF (125 mL, 380 mmol) at 0° C. The reaction mixture was stirred for 1 hour at 0° C., and was quenched with cold aqueous ammonium chloride solution (150 mL). The organic layer was separated and concentrated under reduced pressure. The residue was re-dissolved in ethyl acetate (100 mL). The aqueous layer was diluted with water (100 mL) and was extracted with ethyl acetate (3×50 mL). The organic extracts were combined, washed with brine, and dried over magnesium sulfate. Filtration and concentration under reduced pressure gave the product (48.4 g) which was used in the next reaction step without further purification.

1. customwas quenched with cold aqueous ammonium chloride solution (150 mL)
2. customThe organic layer was separated
3. concentrationconcentrated under reduced pressure
4. dissolutionThe residue was re-dissolved in ethyl acetate (100 mL)
5. additionThe aqueous layer was diluted with water (100 mL)
6. extractionwas extracted with ethyl acetate (3×50 mL)
7. washwashed with brine
8. dry with materialdried over magnesium sulfate
9. filtrationFiltration and concentration under reduced pressure