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

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+).

1. customdid not rise above 0° C
2. customthe reaction now at 0° C.
3. customwas quenched with saturated NH4Cl (100 mL) slowly
4. additionThe mixture was diluted with 400 mL water and 100 mL EtOAc
5. customthe layers were separated
6. extractionThe aqueous layer was extracted with EtOAc (2×300 mL)
7. dry with materialThe combined EtOAc extracts were dried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated
10. customto give a dark residue, which
11. custompurified
12. custom0-25% ethyl acetate/hexanes (30 min), 25% (15 min)
13. washProduct began eluting at 33 minutes
14. concentrationProduct fractions were concentrated

ORD record

ord-fa518d49851d488fad4de508bf41020e

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09187464B2