Methyl chloroformate → (3-Bromopyridin-4-yl)methanol

Temperature

0 °C

To a mixture of 3-bromoisonicotinic acid (2.5 g, 12.37 mmol, 1 eq.) and TEA (3.44 mL, 24.75 mmol, 2.0 eq.) in THF (100 mL) was added methyl chloroformate (1.2 mL, 14.85 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 (0.95 g, 24.75 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, 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-bromopyridin-4-yl)methanol (1.2 g, 52%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 8.48 (s, 1H), 8.37 (d, J=4.9 Hz, 1H), 7.37 (d, J=4.9 Hz, 1H), 4.61 (d, J=5.5 Hz, 2H), 2.3 (t, J=5.5 Hz, 1H). LRMS (M+H+) m/z 188.0.

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-9fc6d4a9873d435d9c237c0805651b64

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09012450B2