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

Participants

Reaction Conditions

Reaction Steps

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.

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