2,6-Dimethylpyrazine → 2-[(E)-2-(3-fluorophenyl)ethenyl]-6-methylpyrazine

Participants

Reaction Conditions

Reaction Steps

2,6-Dimethylpyrazine (5.0 g, 46 mmol) was dissolved in THF (200 mL) and cooled to 0° C. Potassium t-butoxide (46 mL of a 1.0M solution in THf, 46 mmol) was added to afford a dark red solution. The solution was allowed to warm to ambient temperature and stir for 1 hr. The solution was then cooled to 0° C., and 3-fluorobenzaldehyde (4.9 mL, 46 mmol) was added via syringe pump over 2 h. The reaction was then allowed to slowly warm to ambient temperature. After stirring at ambient temperature for 18 h, the reaction mixture was cooled to 0° C. and quenched by the addition of concentrated aqueous HCl (10 mL). The resulting suspension was allowed to warm to ambient temperature for 15 minutes, then cooled to 0° C. and brought to pH=8 by addition of solid NaHCO3. The layers were separated, and the aqueous layer was extracted with ethyl acetate (3.times.200 mL). The combined organic layers were washed with brine (200 mL), dried over MgSO4, filtered, and concentrated in vacuo. The crude product was purified by column chromatography eluting with 90:10, 85:15, then 80:20 hexane:ethyl acetate to afford 2-[(E)-2-(3-fluorophenyl)ethenyl]-6-methylpyrazine (4.14 g, 42% yield) as a light yellow solid. M.p. 43-44° C. 1H NMR (CDCl3, 300 MHz) Δ8.44 (s, 1H), 8.31 (s, 1H), 7.29 (d, J=16 Hz, 1H), 7.37-7.26 (m, 3H), 7.12 (d, J=16 Hz, 1H), 7.05-6.98 (m, 1H), 2.59 MS (ESI) 214.5 (M+). This material was carried on to the next step without further purification.

Provenance & Evidence