Br[C:2](P(=O)(OCC)OCC)([F:4])[F:3].C(=O)=O.CC(C)=O.[I:20][C:21]1[C:29]2[C:24](=[CH:25][CH:26]=[C:27]([OH:30])[CH:28]=2)[N:23]([CH3:31])[N:22]=1.[OH-].[K+]>CC#N.O.CCOC(C)=O>[F:3][CH:2]([F:4])[O:30][C:27]1[CH:28]=[C:29]2[C:24](=[CH:25][CH:26]=1)[N:23]([CH3:31])[N:22]=[C:21]2[I:20]
Diethyl bromodifluoromethylphosphonate (9 g, 10.9 mmol) was added in one portion to a cooled (dry ice-acetone bath) solution of 3-iodo-1-methyl-1H-indazol-5-ol (3 g, 37.8 mmol) and KOH (15 g, 267 mmol) in CH3CN (50 mL) and H2O (50 mL) with stirring, the reaction mixture was warmed to room temperature and stirred for 0.5 h, the mixture was diluted with EtOAc (50 mL), The organic layer was washed with H2O (50 mL), brine (100 mL), dried over Na2SO4 and concentrated under reduced pressure, the residue was purified by column chromatography (silica gel, 200-300 mesh, eluting with petroleum ether/EtOAc=3:1) to give 5-(difluoromethoxy)-3-iodo-1-methyl-1H-indazole (1.85 g, 53%) as a white solid. LCMS: (M+H)+=325; 1H NMR (300 MHz, CDCl3), δ 7.36-7.33 (m, 1H), 7.28-7.23 (m, 1H), 7.19 (s, 1H), 6.53 (t, 1H, J=73.5 Hz), 4.09 (s, 3H).
Wird geladen…
