Diisopropylethylamine → (2R)-4-[3-(2-fluoro-3-methoxyphenyl)isoxazol-5-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Participants

Reaction Steps

N,N-Dimethy-4-aminopyridine (0.04 g, 0.3 mmol, 0.3 equiv), N-ethyl-N-isopropylpropan-2-amine (0.89 mL, 5.2 mmol, 4.5 equiv), T3P® (50% w/w solution in ethyl acetate, 2.7 mL, 4.5 mmol, 4.0 equiv), and (2R)-4-[3-(2-fluoro-3-methoxyphenyl)isoxazol-5-yl]-2-methyl-2-(methylsulfonyl)butanoic acid (0.42 g, 1.1 mmol, 1.0 equiv) were allowed to stir at room temperature for 30 min. A solution of O-(tetrahydro-2H-pyran-2-yl)hydroxylamine (0.15 g, 1.2 mmol, 1.2 equiv) in ethyl acetate (12 mL) was added, and the reaction was allowed to stir overnight (18 h) at room temperature. Water (40 mL) was added, and the mixture was extracted with ethyl acetate (2×50 mL). The combined organic phases were dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography (25 g silica gel column, 0-100% gradient ethyl acetate in hexanes) to provide (2R)-4-[3-(2-fluoro-3-methoxyphenyl)isoxazol-5-yl]-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide as a tan solid (0.23 g, 42%). MS (LCMS) m/z 469.1 (M−1).

Provenance & Evidence