Methyl chloroformate → (3-Chloropyrazin-2-yl)methanol

Temperature

0 °C

To a solution of 3-chloropyrazine-2-carboxylic acid (2.0 g, 12.70 mmol, 1.0 eq.) and TEA (3.50 mL, 25.40 mmol, 2.0 eq.) in THF (50 mL) was added methyl chloroformate (1.2 mL, 15.20 mmol, 1.2 eq.) at 0° C. The mixture was stirred at 0° C. for 10 min and filtered. To this filtrate was added a suspension of NaBH4 (0.97 g, 25.40 mmol, 2 eq.) in water (1.0 mL) at 0° C. The mixture was stirred at 0° C. for 1 h, quenched with NH4Cl(aq) solution, and extracted with EtOAc twice. The combined organic layers were dried over Na2SO4, concentrated, and purified on silica gel using a mixture of EtOAc and hexanes as eluent to give (3-chloropyrazin-2-yl)methanol (400 mg, 22%) as a white solid. 1H NMR (400 MHz, MeOD) δ 8.58 (d, J=2.5 Hz, 1H), 8.38 (d, J=2.5 Hz, 1H), 4.84 (s, 2H). LRMS (M+H+) m/z 145.1.

1. filtrationfiltered
2. additionTo this filtrate was added
3. stirringThe mixture was stirred at 0° C. for 1 h
4. customquenched with NH4Cl(aq) solution
5. extractionextracted with EtOAc twice
6. dry with materialThe combined organic layers were dried over Na2SO4
7. concentrationconcentrated
8. custompurified on silica gel using
9. additiona mixture of EtOAc and hexanes as eluent

ORD record

ord-2b11664989d24ded85fd1d515b5d0831

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09012450B2