反应详情

To a solution of diisopropylamine (3.0 mL, 21.40 mmol) in THF (10 mL) at −78° C. was added n-BuLi (7.6 mL, 17.84 mmol). After 30 min, a solution of 2-bromopyridine (1.1 mL, 11.89 mmol) in THF (30 mL) was added and stirring was continued at −78° C. After 45 min, cyclobutanone (1.0 g, 14.27 mmol) was added and the mixture was stirred at −78° C. for 1.5 h. After warming to room temperature, the mixture was quenched with water (20 mL), diluted with saturated NH4Cl (15 mL), and extracted with Et2O (3×30 mL). The combined organic layer was dried (MgSO4), filtered, and concentrated to afford an orange oil. Purification by flash column chromatography on silica gel using hexanes/EtOAc (2:1) afforded 1-(2-bromo-pyridin-3-yl)-cyclobutanol as an orange oil (1.0 g, 37%). 1H NMR (CDCl3) δ 1.69-1.73 (m, 1H), 2.19-2.22 (m, 1H), 2.49-2.55 (m, 2H), 2.61-2.68 (m, 2H), 3.01 (s, 1H), 7.29 (dd, 1H, J=5.1, 4.8 Hz), 7.68 (dd, 1H, J=7.7, 2.1 Hz), 8.28 (dd, 1H, J=4.7, 1.8 Hz).

1. customwas continued at −78° C
2. waitAfter 45 min
3. stirringthe mixture was stirred at −78° C. for 1.5 h
4. customthe mixture was quenched with water (20 mL)
5. additiondiluted with saturated NH4Cl (15 mL)
6. extractionextracted with Et2O (3×30 mL)
7. dry with materialThe combined organic layer was dried (MgSO4)
8. filtrationfiltered
9. concentrationconcentrated
10. customto afford an orange oil
11. customPurification by flash column chromatography on silica gel