2,2,2-Trifluoroethanol → 2-(2,2,2-Trifluoroethoxy)pyridine-4-carboxylic acid

2-Chloropyridine-4-carboxylic acid (200 mg, 1.27 mmol), potassium tert-butoxide (381 mg, 3.81 mmol) and 2,2,2-trifluoroethanol (2.6 mL) were charged to a sealed tube under nitrogen and stirred at 170 C for 3 h. 2,2,2-Trifluoroethanol (1 mL) was added and the reaction stirred at 170 C for 17 h. The mixture was evaporated under vacuum and the residue was dissolved in water (5 mL). 2M HCl was added to bring the solution to pH 5 and the mixture was extracted with DCM (3×10 mL). 2M HCl was then added to the aqueous layer to bring the solution to pH 3 and the mixture was extracted with DCM (4×6 mL). The combined organic extractions were washed with brine (5 mL), dried over sodium sulfate and evaporated under vacuum to afford the title compound as a white solid (210 mg, 75%). Method C HPLC-MS: MH+ requires m/z=222. Found: m/z=222, Rt=1.26 min (95%).

1. stirringthe reaction stirred at 170 C for 17 h
2. customThe mixture was evaporated under vacuum
3. dissolutionthe residue was dissolved in water (5 mL)
4. addition2M HCl was added
5. extractionthe mixture was extracted with DCM (3×10 mL)
6. addition2M HCl was then added to the aqueous layer
7. extractionthe mixture was extracted with DCM (4×6 mL)
8. extractionThe combined organic extractions
9. washwere washed with brine (5 mL)
10. dry with materialdried over sodium sulfate
11. customevaporated under vacuum

ORD record

ord-c9daf0177b2341af866e225f4e43ba0f

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08895733B2