Hydrochloric Acid → 6-(2,2,2-Trifluoroethoxy)pyridine-2-carboxylic acid

6-Chloropyridine-2-carboxylic acid (1.00 g, 6.347 mmol), 2,2,2-trifluoroethan-1-ol (0.683 mL, 9.520 mmol) and potassium hydroxide (1.424 g, 25.387 mmol) were dissolved in DMSO (25 mL) and heated at 100 C for 18 h. The reaction mixture was re-treated with potassium hydroxide (0.356 g, 6.347 mmol) and heated at 100 C for 18 h. The reaction mixture was then re-treated with 2,2,2-trifluoroethan-1-ol (1.367 mL, 19.040 mmol) and potassium hydroxide (0.356 g, 6.347 mmol) and heated at 110 C for 18 h. The reaction mixture was then further re-treated with potassium hydroxide (0.356 g, 6.347 mmol) and 2,2,2-trifluoroethan-1-ol (0.683 mL, 9.520 mmol) and the mixture was stirred at room temperature for 72 h. Water (10 mL) was added and acidified to pH 1 with 1M hydrochloric acid. The aqueous was extracted with EtOAc (3×15 mL) and the organic layer was washed with brine (15 mL). This was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give a brown gum. The crude material was purified by FCC (DCM: MeOH, 90:10) to afford the title compound as a yellow solid (1.26 g, 90%). Method B HPLC-MS: MH+ requires m/z=222 Found: m/z=222, Rt=1.71 min (79%).

1. temperatureheated at 100 C for 18 h
2. temperatureheated at 100 C for 18 h
3. temperatureheated at 110 C for 18 h
4. extractionThe aqueous was extracted with EtOAc (3×15 mL)
5. washthe organic layer was washed with brine (15 mL)
6. dry with materialThis was dried over anhydrous sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customto give a brown gum
10. customThe crude material was purified by FCC (DCM: MeOH, 90:10)

ORDレコード

ord-f2d25fd62db2441392d2531d6a60a9de

出典データセット

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08895733B2