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0 °C

A stirred suspension of 4-{4-[6-bromo-2-oxo-5-(trifluoromethyl)-2,3-dihydro-1H-benzimidazol-1-yl]-1-piperidinyl}tetrahydro-2H-pyran-4-carbonitrile (D70, 1100 mg, 0.21 mmol) in tetrahydrofuran (8 ml) at room temperature under argon was treated with 3M methylmagnesium bromide solution in diethyl ether (0.15 ml, 0.46 mmol) and the insoluble material rapidly dissolved. Further methylmagnesium bromide solution was added after a total of 50 minutes (0.15 ml) and a total of 70 minutes (0.20 ml). After another 15 minutes the reaction mixture was cooled to 0° C. and treated dropwise with 1M aq. NH4Cl solution (3 ml), then diluted with water (15 ml) and extracted with ethyl acetate. The extract was washed with brine, dried (Na2SO4) and concentrated under vacuum to afford the title compound as a white solid. This was converted to its HCl salt as a white solid (95 mg, 90%).

1. dissolutionthe insoluble material rapidly dissolved
2. customa total of 70 minutes (0.20 ml)
3. extractionextracted with ethyl acetate
4. washThe extract was washed with brine
5. dry with materialdried (Na2SO4)
6. concentrationconcentrated under vacuum