Diethyl Ether → 1-(pyridin-2-yl)butan-1-one

A solution of 2-cyanopyridine (2.20 g, 21.13 mmol) in Et2O (35 mL) added over 10 min to a rapidly stirring solution of freshly prepared n-PrMgBr (from n-PrBr (2.71 g, 22.03 mmol) and Mg (0.62 g) in Et2O (35 mL). Once addition was completed, the reaction was heated to reflux in a warm water bath for 2.5 hours. The reaction was cooled to RT then placed in ice, quenched with 5 mL H2O followed by 60 mL 5N H2SO4. The ether phase was separated. The aqueous phase was heated in warm water for 15 minutes, then cooled in ice, basified with sat. K2CO3. The mixture was extracted with CHCl3 and dried over K2CO3. The solution was filtered, concentrated and purified on Biotage Horizon (10-100% A=Hex, B=2:1 Hex:EtOAc) to afford 1.16 g of 1-(pyridin-2-yl)butan-1-one as an oil: 1H NMR (400 MHz, CDCl3) δ ppm 8.67 (ddd, J=4.74, 1.71, 0.88 Hz, 1H), 8.03 (dt, J=7.83, 1.01 Hz, 1H), 7.82 (td, J=7.71, 1.77 Hz, 1H), 7.45 (ddd, J=7.52, 4.74, 1.14 Hz, 1H), 3.15-3.21 (m, 2H), 1.71-1.80 (m, J=7.43, 7.43, 7.43, 7.43, 7.43 Hz, 2H), 1.00 (t, J=7.33 Hz, 3H).

1. additionOnce addition
2. temperaturethe reaction was heated
3. temperatureto reflux in a warm water bath for 2.5 hours
4. customquenched with 5 mL H2O
5. customThe ether phase was separated
6. temperatureThe aqueous phase was heated in warm water for 15 minutes
7. temperaturecooled in ice
8. extractionThe mixture was extracted with CHCl3
9. dry with materialdried over K2CO3
10. filtrationThe solution was filtered
11. concentrationconcentrated
12. custompurified on Biotage Horizon (10-100% A=Hex, B=2:1 Hex:EtOAc)

ORD record

ord-cbffcd7f1d44474dbd0567fbe3d69cec

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08148400B2