Diisopropylamine → 1-(2-Bromopyridin-3-yl)cyclobutanol

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

ORD record

ord-9b0de04a9a674c5488e62ea57539cacd

Source dataset

uspto-grants-2007_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07291631B2