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

Temperature

-78 °C

A solution of 2-chloropyridine (XI) (9.39 mL, 0.1 mol) in, anhydrous THF (50 mL) was added slowly to a solution of LDA (2.0 M solution in THF/hexane/ethylbenzene, 50 mL, 0.1 mol) in THF (200 mL) stirred at −78° C. under nitrogen. The stirring was continued at −78° C. for an additional 3 h before adding acetaldehyde (6.17 mL, 0.110 mol). The solution was stirred at −78° C. for another 2 h before allowing the temperature to rise to −40° C. A solution of water (4 mL) in THF (40 mL) was added slowly to the solution. When the temperature reached −10° C., additional water (200 mL) was added to the solution. The solution was extracted with ethyl ether (3×100 mL). The combined organic phase was dried over MgSO4, filtered and evaporated under reduced pressure to get a brown viscous residue. The crude product was purified on a flash silica gel column (1:1 DCM:hexane→100% DCM) to produce 1-(2-chloropyridin-3-yl)ethanol (XII) as a brown viscous oil (6 g, 38.1 mmol, 38% yield). 1H NMR (CDCl3) δ ppm 1.52 (d, J=6.41 Hz, 3H), 2.51 (brs, 1H), 5.24 (m, 1H), 7.28 (m, 1H), 7.97 (dd, J=7.72 Hz, J=1.70 Hz, 1H), 8.27 (dd, J=7.72 Hz, J=1.79 Hz, 1H).

1. stirringThe solution was stirred at −78° C. for another 2 h
2. customto rise to −40° C
3. customreached −10° C.
4. extractionThe solution was extracted with ethyl ether (3×100 mL)
5. dry with materialThe combined organic phase was dried over MgSO4
6. filtrationfiltered
7. customevaporated under reduced pressure
8. customto get a brown viscous residue
9. customThe crude product was purified on a flash silica gel column (1:1 DCM:hexane→100% DCM)

ORD record

ord-fbaf43fd51fb42888d0671a8437ee8e0

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08883822B2