Acetic Acid → (r)-2-(3,4-Difluorophenyl)-4-(3-hydroxy-1-butoxy)-5-[4-(methylsulfonyl)phenyl]-3(2h)-pyridazinone

Participants

Reaction Steps

A stirred solution of the product from step Example 545D(˜2 mmol) in acetone (10 mL) was chilled to 0° C. To this was added 32% peracetic acid in acetic acid solution (1.42 mL, 6 mmol). The reaction mixture was stirred for 1 hour while warming to room temperature. At this point the oxidation was complete, but some of the product's hydroxy group was still silylated so 1M tetrabutylammonium fluoride in THF (4 mL, 4 mmol) was added and stirring was continued for 0.5 hours. The reaction mixture was then treated with 5% aqueous sodium thiosulfate solution (30 mL) for 2 hours. The precipitated product was collected by filtration, washed with water (10 mL) and hexane (10 mL). The solid was stirred in isopropanol (5 mL) for 6 hours then collected by filtration and dried to provide the title compound (0.78 g, 87%). mp 126–129° C.; 1H NMR (300 MHz, CDCl3) δ 1.22 (d, J=6 Hz, 3H), 1.62–1.74 (m, 1H), 1.84–1.94 (m, 1H), 3.16 (s, 3H), 3.30 (s br, 1H), 4.00–4.10 (m, 1H), 4.20–4.30 (m, 1H), 4.63 (td, J=9.6 Hz, J=4 Hz, 1H), 7.25–7.34 (m, 1H), 7.46–7.52 (m, 1H), 7.56–7.64 (m, 1H), 7.78–7.84 (m, 2H), 7.97 (s, 1H), 8.06–8.12 (m, 2H); MS (DCI/NH3) m/z 468 (M+NH4)+.

Provenance & Evidence