Methyl isobutyrate → Tert-butyl 2-(3-chloropyrazin-2-yl)-2-methylpropanoate

Sodium tert-butoxide (7.2 g, 74.9 mmol) was suspended in diethyl ether (2500 mL) under argon. Methyl isobutyrate (6.0 ml, 58.7 mmol) was added and the mixture stirred at room temperature for 3 hours. The suspension was filtered through a pad of neutral alumina and concentrated under reduced pressure to −50 mL. The crude product was placed under argon and bromo[tri-tert-butylphosphine]dipalladium(1)dimer (0.282 g, 0.363 mmol) was added. The solution was cooled in an ice/acetone bath and lithium bis(trimethylsilyl)amide (1.0 M solution in tetrahydrofuran, 55 ml, 55.0 mmol) was added. The solution was stirred for minutes. 2,3-Dichloropyrazine (5.0 ml, 48.0 mmol) was added neat and after another 5 minutes the mixture was heated at 50° C. for 40 hours. The mixture was cooled and partitioned between water (400 mL), saturated ammonium chloride (100 mL) and ethyl acetate (400 mL). The organic was dried with magnesium sulfate and evaporated to dryness under reduced pressure. The crude product was purified using silica chromatography (hexane to ethyl acetate gradient) to give tert-butyl 2-(3-chloropyrazin-2-yl)-2-methylpropanoate (8.51 g, 33.1 mmol, 69.0% yield).

1. filtrationThe suspension was filtered through a pad of neutral alumina
2. concentrationconcentrated under reduced pressure to −50 mL
3. temperatureThe solution was cooled in an ice/acetone bath
4. stirringThe solution was stirred for minutes
5. temperaturewas heated at 50° C. for 40 hours
6. temperatureThe mixture was cooled
7. custompartitioned between water (400 mL), saturated ammonium chloride (100 mL) and ethyl acetate (400 mL)
8. dry with materialThe organic was dried with magnesium sulfate
9. customevaporated to dryness under reduced pressure
10. customThe crude product was purified

ORD record

ord-7f3c7b07cbef49e69e33e51055dab6cd

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09174992B2