反应详情

Dissolve 6-(trifluoromethyl)pyridine-3-carboxylic acid (0.949 g, 4.767 mmol) in DMF (10 mL) and add N,O-dimethylhydroxylamine hydrochloride (0.590 g, 5.959 mmol), and DIPEA (1.67 mL, 9.534 mmol), followed by BOP (2.259 g, 5.005 mmol). Stir the resulting mixture for about 60 hours. Pour reaction mixture into water (200 mL). Extract with EtOAc (4×75 mL). Wash the combined organic extracts with a saturated sodium chloride aqueous solution (5×75 mL). Dry the organic extracts over sodium sulfate; filter; collect the filtrate; and concentrate the filtrate under reduced pressure. Dissolve the residue in EtOAc (100 mL). Sequentially wash the residue in EtOAc with a saturated NaHCO3 aqueous solution (50 mL) to remove any residual acid starting material, followed by water (2×50 mL), and then a saturated sodium chloride aqueous solution (2×50 mL). Dry the organic layer over sodium sulfate; filter; collect the filtrate; and concentrate the filtrate under reduced pressure to give the title compound as a clear liquid (1.04 g, 93% yield). 1H NMR (400.43 MHz, d6-DMSO) δ 8.90 (d, J=2.0 Hz, 1H), 8.25-8.23 (m, 1H), 7.96 (dd, J=0.7, 8.1 Hz, 1H), 3.52 (s, 3H), 3.27 (s, 3H).

1. additionPour
2. extractionExtract with EtOAc (4×75 mL)
3. washWash the combined organic extracts with a saturated sodium chloride aqueous solution (5×75 mL)
4. dry with materialDry the organic extracts over sodium sulfate
5. filtrationfilter
6. customcollect the filtrate
7. concentrationand concentrate the filtrate under reduced pressure
8. dissolutionDissolve the residue in EtOAc (100 mL)
9. washSequentially wash the residue in EtOAc with a saturated NaHCO3 aqueous solution (50 mL)
10. customto remove any residual acid
11. dry with materialDry the organic layer over sodium sulfate
12. filtrationfilter
13. customcollect the filtrate
14. concentrationand concentrate the filtrate under reduced pressure