Hydrochloric Acid → [3-Fluoro-2-(trifluoromethyl)pyridin-4-yl]methanol

Carbonyldiimidazole (1.16 g, 7.17 mmol) was added to a solution of 3-fluoro-2-trifluoromethyl-isonicotinic acid (1.00 g, 4.78 mmol) in THF (13.7 mL). The reaction mixture was stirred at RT overnight and was then added to a cold (0° C.) solution of NaBH4 (0.905 g, 23.9 mmol) in water (34.2 mL). The mixture was stirred for 10 min at 0° C., and 1M HCl was then added carefully (caution: H2 evolving). Volatiles were removed under reduced pressure, and the residue was dissolved in saturated aqueous NaHCO3. The mixture was extracted repeatedly with CH2Cl2, the combined organics were dried (phase separator) and concentrated in vacuo. Purification by flash column chromatography on silica gel (eluent gradient: c-hexane/EtOAc 1:1 to 0:1) afforded the title compound as a yellow oil. TLC, Rf (c-hexane/EtOAc 1:1)=0.27; MS (LC/MS): 196.0 [M+H]+; tR (HPLC conditions b): 2.62 min.

1. stirringThe mixture was stirred for 10 min at 0° C.
2. customVolatiles were removed under reduced pressure
3. dissolutionthe residue was dissolved in saturated aqueous NaHCO3
4. extractionThe mixture was extracted repeatedly with CH2Cl2
5. customthe combined organics were dried (phase separator)
6. concentrationconcentrated in vacuo
7. customPurification by flash column chromatography on silica gel (eluent gradient: c-hexane/EtOAc 1:1 to 0:1)

ORD record

ord-692b8e5207b6449ea85f4a2644e2e755

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09085555B2