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

関与物質

反応手順

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%).

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