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

Temperature

-78 °C

2,3-Dibromopyridine (2.30 g, 9.7 mmol) in tetrahydrofuran (10 mL) was added to a solution of isopropyl magnesium chloride/lithium chloride (1M in tetrahydrofuran, 10 mL, prepared according to the method of Krasovskiy and Knochel, Angew. Chem. Int. Ed. 2004, 43, 3333-3336) at approximately −15° C. under nitrogen. This mixture was cooled to −78° C. and cyclobutanone (0.74 mL, 9.9 mmol) added. It was stirred for 1 hour before allowing to warm to 0° C. for a further 1 hour then quenched with saturated ammonium chloride solution. Water (150 mL) was added and extracted with diethyl ether (2×75 mL). These extracts were washed with water and brine then dried (MgSO4), filtered and the solvent removed in vacuo. Purification by flash column chromatography eluting with a 0-10% diethyl ether/dichloromethane gradient gave 1-(2-bromopyridin-3-yl)cyclobutanol (0.57 g, 26%). 1H NMR (400 MHz, CDCl3) δ 8.28 (1H, dd, J=1.9, 4.7 Hz), 7.68 (1H, dd, J=1.9, 7.6 Hz), 7.30-7.26 (1H, m), 3.00 (1H, s), 2.70-2.60 (2H, m), 2.55-2.47 (2H, m), 2.30-2.16 (1H, m), 1.77-1.65 (1H, m); m/z (ES+) 228, 230 [MH+].

1. custom10 mL, prepared
2. customat approximately −15° C.
3. temperatureto warm to 0° C. for a further 1 hour
4. customthen quenched with saturated ammonium chloride solution
5. additionWater (150 mL) was added
6. extractionextracted with diethyl ether (2×75 mL)
7. washThese extracts were washed with water and brine
8. dry with materialthen dried (MgSO4)
9. filtrationfiltered
10. customthe solvent removed in vacuo
11. customPurification by flash column chromatography
12. washeluting with a 0-10% diethyl ether/dichloromethane gradient

ORD record

ord-311a193c998c48358280d37447d25d56

Source dataset

uspto-grants-2009_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07592456B2