Hydrogen Peroxide → 5-(2,4-difluorophenoxy)-1-isobutyl-1H-indazol-6-ol

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Reaction Steps

(15d; prepared according to Example 110, Steps A-E: 6-Bromo-5-(2,4-difluorophenoxy)-1-isobutyl-1H-indazole (1.36 g, 3.6 mmol) was dissolved in dry ether (17.5 mL) and cooled to −78° C. n-Butyl lithium (1.7 mL of 2.5 M in hexane) was added dropwise over 10 minutes and the mixture was stirred for 30 minutes. Trimethylborate (6 mL, 53.5 mmol) was added drop-wise over 10 minutes and the reaction mixture was allowed to warm to room temperature and stir for 18 hours. The mixture was cooled to −10° C. and 2N NaOH (3.6 mL) and water (3 mL) were added followed by H2O2 (3.6 mL) and 2N NaOH (3.6 mL). The reaction mixture was stirred at room temperature for 2 hours when white precipitate formed. Water (3 mL), 4N NaOH (4 mL), and H2O2 (1 mL) was added and the mixture stirred for another 20 minutes. The mixture was then diluted with ether and the layers separated. The aqueous layer was washed with ether, acidified and then extracted with ether (2×). The combined ether extracts were washed with water and brine, dried over Na2SO4 and concentrated under reduced pressure to afford 0.465 g product (41% yield).

Provenance & Evidence