反应详情

To a solution of 4-(4-hydroxytetrahydro-2H-pyran-4-yl)benzonitrile (Step 1 of Intermediate I, 300 mg, 1.48 mmol) in DMF (6.5 mL) was added sodium hydride (60% suspension in mineral oil, 65 mg, 1.62 mmol) at a temperature of ˜5° C. The reaction mixture was allowed to stirr for 1 h at this temperature, before methyl iodide (110 μL, 1.77 mmol) was added. Stirring was continued over night at rt. The mixture was diluted with water and extracted with diethyl ether. The organic extract was dried with anhydrous magnesium sulfate and filtered. After evaporation of the solvent, the crude product was purified by MPLC (silica, cyclohexane/ethyl acetate 20:1→4:1) to afford the title compound in pure form (238 mg, 74%): 1H NMR (500 MHz, CDCl3) δ 7.68 (d, 2H), 7.51 (d, 2H), 3.89-3.82 (m, 4H), 2.99 (s, 3H), 2.03-1.98 (m, 2H), 1.94-1.91 (m, 2H); DCI(NH3)-MS m/z 235 (M+NH4)+; HPLC RT (Method I) 3.99 min.

1. additionwas added
2. waitwas continued over night at rt
3. extractionextracted with diethyl ether
4. extractionThe organic extract
5. dry with materialwas dried with anhydrous magnesium sulfate
6. filtrationfiltered
7. customAfter evaporation of the solvent
8. customthe crude product was purified by MPLC (silica, cyclohexane/ethyl acetate 20:1→4:1)