3,3,3-Trifluoro-1-propanol → HCID 66803378, compound

3,3,3-Trifluoropropanol (0.338 g, 2.96 mmol) was dissolved in THF (5 mL) and cooled to 0 C under nitrogen. Potassium tert-butoxide (0.332 g, 2.96 mmol) was added and the mixture stirred for 5 min. Ethyl 6-chloronicotinate (0.500 g, 2.69 mmol) was added, the mixture was warmed to room temperature and stirred for 3 h. Brine (10 mL) was added and the mixture extracted with EtOAc (3×10 mL). The combined organic layers were dried over sodium sulfate and concentrated to yield a yellow oil. This was purified by FCC, eluting with a gradient of 0-10% EtOAc in heptane to afford the title compound as a colourless oil (0.240 g, 34%), which was used in the next step without further purification. NMR shows approximately 15% unreacted ethyl 6-chloronicotinate. 1H NMR (500 MHZ, MeOH-d4) δ ppm 8.75 (1H, d), 8.11 (1H, dd), 6.71 (1H, d), 4.55 (2H, t), 4.31 (2H, q), 2.57 (2H, m) and 1.33 (3H, t).

1. temperaturecooled to 0 C under nitrogen
2. stirringstirred for 3 h
3. extractionthe mixture extracted with EtOAc (3×10 mL)
4. dry with materialThe combined organic layers were dried over sodium sulfate
5. concentrationconcentrated
6. customto yield a yellow oil
7. customThis was purified by FCC
8. washeluting with a gradient of 0-10% EtOAc in heptane

ORD record

ord-436eab75b2c84831afa76b1a4e96c7c6

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08895733B2