Acetaldehyde → 1-(2-bromopyridin-3-yl)ethanol

Temperature

-78 °C

Butyllithium (1.6M in hexanes, 26.7 mL, 42.7 mmol) was added over 15 minutes to a solution of diisopropylamine (6.0 mL, 42.8 mmol) in tetrahydrofuran (45 mL) at 0 to 5° C. under nitrogen, then stirred for 30 minutes. This solution was cooled to −78° C. and 2-bromopyridine (3.45 mL, 35.8 mmol) was added. The reaction was stirred at −78° C. for 1 hour. Acetaldehyde (2 mL, 35.6 mmol) was added and the reaction stirred at −78° C. for 1 hour then quenched with saturated ammonium chloride solution and allowed to warm to room temperature. The reaction mixture was diluted with water and extracted with ethyl acetate (x3). The combined organic layers were washed with water and brine, dried over MgSO4 and evaporated in vacuo. The residue was purified by flash column chromatography on silica, eluting with 0-10% diethyl ether/dichloromethane, to give 1-(2-bromopyridin-3-yl)ethanol (2.65 g, 37%). 1H NMR (400 MHz, CDCl3) δ8.27 (1H, dd, J=2.0, 4.7 Hz), 7.92 (1H, dd, J=2.0, 7.4 Hz), 7.31 (1H, dd, J=4.7, 7.8 Hz), 5.19 (1H, q, J=6.3 Hz), 2.18 (1H, s), 1.51 (3H, d, J=6.4 Hz).

1. stirringThe reaction was stirred at −78° C. for 1 hour
2. stirringthe reaction stirred at −78° C. for 1 hour
3. customthen quenched with saturated ammonium chloride solution
4. temperatureto warm to room temperature
5. additionThe reaction mixture was diluted with water
6. extractionextracted with ethyl acetate (x3)
7. washThe combined organic layers were washed with water and brine
8. dry with materialdried over MgSO4
9. customevaporated in vacuo
10. customThe residue was purified by flash column chromatography on silica
11. washeluting with 0-10% diethyl ether/dichloromethane

ORD record

ord-3f9657c711b34451a24a27e0d0b12add

Source dataset

uspto-grants-2009_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07592456B2