Hydrogen Peroxide → 8-fluoro-3-(3-hydroxypropyl)-N-methoxy-N-methyl-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-carboxamide

Participants

Reaction Conditions

Reaction Steps

3-Allyl-8-fluoro-N-methoxy-N-methyl-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-carboxamide (5-6; a racemic mixture, 3.7 g, 9.35 mmol) was dissolved in anhydrous THF (50 mL) and treated with a 0.5M solution of 9-BBN (37.4 mL, 18.7 mmol) and stirred at 50° C. for 2 h. The reaction was cooled to 0° C. and treated with 3N NaOH (5 mL) and 30% H2O2 in water (5 mL), and stirred an additional hour. Upon completion, the reaction was treated with brine (50 mL), and extracted with EtOAc (3×100 mL). The combined organic extracts were dried (MgSO4), filtered and concentrated. The crude residue was subjected to flash column chromatography (ISCO Redisep 120 g SiO2 column, 0-100% EtOAc/hexanes gradient) to provide pure 8-fluoro-3-(3-hydroxypropyl)-N-methoxy-N-methyl-3-phenyl-3a,4-dihydro-3H-pyrazolo[5,1-c][1,4]benzoxazine-2-carboxamide (5-7; a racemic mixture): 1H NMR (300 MHz, CDCl3) δ 7.36-7.19 (m, 5H), 7.15 (dd, J=9.6, 2.9 Hz, 1H), 6.78 (dd, J=8.8, 5.1 Hz, 1H), 6.56 (dt, J=8.8, 3.0 Hz, 1H), 4.00 (dd, J=10.5, 3.5 Hz, 1H), 3.91 (s, 3H), 3.76 (m, 2H), 3.56 (dd, J=11.0, 3.3 Hz, 1H), 3.31 (s, 3H), 2.92 (t, J=10.6 Hz, 1H), 2.60 (dt, J=12.1, 4.9 Hz, 1H), 2.42 (dt, J=12.1, 4.9 Hz, 1H), 1.81 (m, 1H), 1.62 (m, 1H); MS (M+H+, C22H24FN3O4) 414.3 found 414.4 required.

Provenance & Evidence