Hydrochloric Acid → 3,5-Dichloro-2-methylpyrazine

Participants

Reaction Conditions

Reaction Steps

To a solution of n-butyllithium (3.8 mL, 2.5M in hexane, 9.4 mmol) in THF (40 mL) cooled to −30° C. under nitrogen was added 2,2,6,6-tetramethylpiperidine (1.7 mL, 10.1 mmol). This solution was allowed to warm to 0° C. over 20 min. and was then cooled to −70° C. A solution of 2,6-dichloropyrazine (1 g, 6.7 mmol) in THF (40 mL) was added dropwise and the resulting brown solution stirred at −70° C. for 30 min. Iodomethane (4.1 mL, 67 mmol) was then added and the solution stirred at −70° C. for a further 45 min after which time a mixture of ethanol (5 mL), THF (5 mL) and 1N HCl (1 mL) was added. The solution was allowed to warm to room temperature and was concentrated under reduced pressure. The residue was dissolved in H2O (50 mL) and the product extracted into dichloromethane (3×30 mL). The combined organic layers were washed with H2O (50 mL) and brine (50 mL) and dried (Na2SO4). The organic layer was concentrated in vacuo and the residue purified by column chromatography eluting with dichloromethane-hexane (1:1) to separate the product as a clear motile oil (820 mg).

Provenance & Evidence