Methyl 6-chloropyridine-3-carboxylate → Methyl 6-[2-(2,2,2-trifluoroethoxy)ethoxy]pyridine-3-carboxylate

2-(2,2,2-Trifluoroethoxy)ethanol (0.462 g, 3.21 mmol) was dissolved in THF (5 mL) and cooled to 0 C. Potassium tert-butoxide (0.360 g, 3.21 mmol) was added, the mixture was stirred for 5 min and methyl 6-chloronicotinate (0.500 g, 2.91 mmol) was added. The mixture was warmed to room temperature and stirred for 3 h. Brine (10 mL) was added and the mixture was extracted with EtOAc (3×20 mL). The combined organic layers were dried over sodium sulfate and concentrated to yield a yellow oil, which was purified by FCC to afford the title compound as a colourless oil (0.453 g, 56%). 1H NMR (500 MHZ, CDCl3) δ ppm 8.73 (1H, d), 8.10 (1H, dd), 6.74 (1H, d), 4.50 (2H, t), 3.93 (2H, t), 3.87 (2H, q) and 3.84 (3H, s).

1. temperaturecooled to 0 C
2. stirringstirred for 3 h
3. extractionthe mixture was extracted with EtOAc (3×20 mL)
4. dry with materialThe combined organic layers were dried over sodium sulfate
5. concentrationconcentrated
6. customto yield a yellow oil, which
7. customwas purified by FCC

ORD record

ord-c2b33853cdd444f3bf5500fb375298fd

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08895733B2