Ethyl Acetate → 2-Chloro-5-[(2,2,2-trifluoroethoxy)methyl]pyridine

(6-Chloropyridin-3-yl)methanol (1.0 g, 6.97 mmol) was dissolved in THF (20 mL), potassium tert-butoxide (0.860 g, 7.66 mmol) was added and the mixture stirred at room temperature. 2,2,2-Trifluoroethyl trifluoromethanesulfonate (1.78 g, 7.66 mmol) was added dropwise with ice cooling and then the mixture stirred at room temperature for 2 h. EtOAc (50 mL) and water (50 mL) were added, the organic layer was separated and the aqueous layer neutralised to pH 6. The aqueous layer was then further extracted with EtOAc (3×20 mL), combined organic layers were dried over sodium sulfate and concentrated to yield a yellow solid. This was purified by FCC, eluting with a gradient of 0-50% EtOAc in heptane to afford the title compound as a colourless oil (0.537 g, 34%). 1H NMR (500 MHZ, CDCl3) δ ppm 8.30 (1H, d), 7.61 (1H, dd), 7.30 (1H, d), 4.61 (2H, s) and 3.82 (2H, q).

1. stirringthe mixture stirred at room temperature for 2 h
2. customthe organic layer was separated
3. extractionThe aqueous layer was then further extracted with EtOAc (3×20 mL)
4. dry with materialwere dried over sodium sulfate
5. concentrationconcentrated
6. customto yield a yellow solid
7. customThis was purified by FCC
8. washeluting with a gradient of 0-50% EtOAc in heptane

ORD record

ord-6ba6ce9d1f0248d690541fa026ff92d6

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08895733B2