Hydrochloric Acid → (2-Chlorophenyl)-(3,5-dichloropyrazin-2-yl)methanol

Temperature

0 °C

To a −20° C. solution of n-butyllithium (2.5 M in hexane, Aldrich, 26.5 mmol) in dry tetrahydrofuran (200 mL) under argon was added 2,2,6,6-tetramethylpiperidine (Aldrich, 11.5 mL, 66.5 mmol, 1.22 eq). The resulting solution was warmed to 0° C. over 0.5 hour period. The solution was then cooled to −78° C., and a solution of 2,6-dichloropyrazine (Aldrich, 8.24 g, 55.3 mmol, 1.0 eq ) in tetrahydrofuran was slowly added via a syringe. After addition was complete, the resulting mixture was stirred at −78° C. for an additional 1 hour after which 2-chlorobenzaldehyde (Aldrich, 9.3 mL, 83 mmole, 1.5 eq) was added drop wise via a syringe. The reaction mixture was stirred for an additional 1 hour, quenched with hydrochloric acid (18 mL, 220 mmol, 4 eq)/ethanol (75 mL)/tetrahydrofuran (90 mL) mixture, and then warmed to room temperature. The reaction mixture was diluted with aqueous saturated sodium bicarbonate solution and extracted with ether. The organic layer was separated and washed with brine, dried over sodium sulfate, filtered, and concentrated to give a crude oil which was purified via chromatography using dichloromethane/hexanes (1:1) as the eluent to give (2-chlorophenyl)-(3,5-dichloropyrazin-2-yl)methanol (12.8 g, 44 mmol, 80% yield). Mass spec, M+1=290.

1. temperatureThe solution was then cooled to −78° C.
2. additionAfter addition
3. additionwas added drop wise via a syringe
4. temperaturewarmed to room temperature
5. extractionextracted with ether
6. customThe organic layer was separated
7. washwashed with brine
8. dry with materialdried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated
11. customto give a crude oil which
12. customwas purified via chromatography

ORD record

ord-d388159f0fd64129bb70d45e65e8e144

Source dataset

uspto-grants-2009_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07566708B2