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

Temperature

-70 °C

Dry THF (400 mL) and n-butyllithium (1.6 M in hexane, 63 mL, 0.1 mol) were introduced into a 1 L flask under nitrogen at −70° C. A solution of dry diisopropylamine (10.1 g, 0.1 mol) in THF (25 mL) was added dropwise to the mixture at −70° C. The mixture was then kept for 1 h at 0° C. and then cooled to −70° C. A solution of 2-chloropyridine (11.3 g, 0.1 mol) in THF (25 mL) was added dropwise to the mixture at −70° C. and the mixture was stirred for 3 h at this temperature. A solution of acetaldehyde (4.85 g, 0.11 mol) in dry THF (50 mL) was then added dropwise and the mixture was kept for 3 h at −70° C. A solution of water (4 mL) in THF (40 mL), acidified by a few drops of concentrated hydrochloric acid, was added to the mixture at −40° C. and then water (200 mL) was introduced at −10° C. Extraction with diethyl ether (3×150 mL), drying over anhydrous sodium sulfate, and evaporation gave a crude product, which was purified by column chromatography to yield an oil (10 g, 64%). *1H NMR (CDCl3) 8.15 (dd, J=5 and 2 Hz, 1H), 7.95 (dd, J=8 and 2 Hz, 1H), 7.20 (dd, J=8 and 5 Hz, 1H), 5.15 (d, J=7 Hz, 1H), 3.90 (s, 1H), 1.45 (d, J=7 Hz, 3H). *NMR values reported in Journal of Chemical Society Perkin Trans 1: Organic and Bio-organic Chemistry, 1990, 9, 2409-2415.

1. waitthe mixture was kept for 3 h at −70° C
2. additionwas added to the mixture at −40° C.
3. extractionExtraction with diethyl ether (3×150 mL)
4. dry with materialdrying over anhydrous sodium sulfate, and evaporation
5. customgave a crude product, which
6. customwas purified by column chromatography

ORD record

ord-69244b86cd8e4288b3de056c61b0e4a0

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08362031B2