Hydrochloric Acid → 6-(2,2-difluoroethoxy)nicotinic acid

Powdered potassium hydroxide (712 mg, 12.7 mmol) was added to a mixture of 6-chloronicotinic acid (500 mg, 3.17 mmol) and 2,2-difluoroethanol (520 mg, 6.35 mmol) in DMSO (15 mL) and the mixture was stirred at 120 C for 14 h. An additional two equivalents of 2,2-difluoroethanol and potassium hydroxide were added and the mixture was heated for 24 h. The mixture was cooled to room temperature, diluted with water (5 mL), acidified with 1N aq. HCl (to pH 1) and extracted with EtOAc (3×50 mL). The combined organic layers were washed with water (2×25 mL) then brine (50 mL) and concentrated under reduced pressure to provide title compound as a beige solid (620 mg, 96%). Method B HPLC-MS: MH+ requires m/z=204. Found: m/z=204, Rt=1.54 min (90%).

1. temperaturethe mixture was heated for 24 h
2. extractionextracted with EtOAc (3×50 mL)
3. washThe combined organic layers were washed with water (2×25 mL)
4. concentrationbrine (50 mL) and concentrated under reduced pressure

ORD-Eintrag

ord-2b7768f1002f4dd59f20f18a65f7dd7b

Quelldatensatz

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08895733B2