Diethyl Ether → 2-(5-Chloropyrazin-2-yl)propan-2-ol

Participants

Reaction Steps

A well-stirring solution of methyl 5-chloropyrazine-2-carboxylate (23.5 g, 136 mmol) in Tetrahydrofuran (THF) (172 ml) under nitrogen was cooled to −10° C. and became a thick tan suspension. Added methylmagnesium bromide, 3M in diethyl ether (100 ml, 300 mmol) slowly making sure the temperature did not rise above 0° C. After 1 hour, the reaction now at 0° C. was quenched with saturated NH4Cl (100 mL) slowly, followed by EtOAc (100 mL), and the dark mixture was stirred overnight. The mixture was diluted with 400 mL water and 100 mL EtOAc, and the layers were separated. The aqueous layer was extracted with EtOAc (2×300 mL). The combined EtOAc extracts were dried over MgSO4, filtered, and concentrated to give a dark residue, which was divided into two batches. Each batch was loaded (with 10% CH2Cl2/cyclohexane) onto a pre-equilibrated (with hexanes) 330 g silica cartridge and purified using normal phase chromatography CISCO): 0-25% ethyl acetate/hexanes (30 min), 25% (15 min). Product began eluting at 33 minutes. Product fractions were concentrated to afford 2-(5-chloropyrazin-2-yl)propan-2-ol (6.232 g, 25%) as a low viscosity orange oil. MS (m/z) 173.1 (M+H+).

Provenance & Evidence