反应详情

To a solution of (R)-1-(3-(hydroxymethyl)piperidin-1-yl)-3-methylbutan-1-one (Example 34c) (145 mg, 0.73 mmol) in THF (15 mL) was added NaH (44 mg, 1.09 mmol, 60% dispersion in mineral oil) at 0° C. The reaction was warmed to room temperature and stirred for 15 minutes, at which time 2-amino-6-fluorobenzonitrile (109 mg, 0.80 mmol) was added. The mixture was heated at 80° C. overnight, quenched with water, concentrated under reduced pressure to remove THF and extracted with EtOAc (3×). The combined extracts were dried over Na2SO4, filtered, concentrated under reduced pressure and purified by flash chromatography on silica gel (EtOAc/hexanes). The residue was further purified by chiral HPLC (normal phase, ethanol/isopropanol/methanol/hexanes) to give the title compound as a white solid (96 mg, 41%). MS 316 (MH+).

1. additionwas added
2. temperatureThe mixture was heated at 80° C. overnight
3. customquenched with water
4. concentrationconcentrated under reduced pressure
5. customto remove THF
6. extractionextracted with EtOAc (3×)
7. dry with materialThe combined extracts were dried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. custompurified by flash chromatography on silica gel (EtOAc/hexanes)
11. customThe residue was further purified by chiral HPLC (normal phase, ethanol/isopropanol/methanol/hexanes)