反应详情

温度

-78 °C

Under nitrogen atmosphere, BuLi (0.58 mL, 0.89 mmol) was added dropwise to a solution of 5-bromo-6-cyclopropylmethoxy-pyridine-2-carboxylic acid (Example 9 d, 0.2 g, 0.74 mmol) in THF (20 mL) at −78° C. The reaction mixture was stirred for 1 h at −78° C. then cyclobutanone (CAN 1191-95-3, 1.11 mL, 1.47 mmol) in THF (3 mL) was added to the above solution at −78° C. The reaction mixture was allowed to warm to ambient temperature and stirred for 1 h. The reaction mixture was then quenched with NH4Cl and the pH was adjusted to 2 by addition of 1 N HCl. The mixture was extracted with ethyl acetate (3×10 mL); the organic layers were combined, washed with brine (2×10 mL) and dried over Na2SO4. The solvent was removed under reduced pressure and the crude product was used for the next step without further purification; MS (EI): m/e=264.1 [M+H]+.

1. temperatureto warm to ambient temperature
2. stirringstirred for 1 h
3. customThe reaction mixture was then quenched with NH4Cl
4. additionthe pH was adjusted to 2 by addition of 1 N HCl
5. extractionThe mixture was extracted with ethyl acetate (3×10 mL)
6. washwashed with brine (2×10 mL)
7. dry with materialdried over Na2SO4
8. customThe solvent was removed under reduced pressure
9. customthe crude product was used for the next step without further purification