Methyl morpholine oxide → HCID 58467978, compound

Participants

Reaction Steps

In a 50 mL round-bottom flask was dissolved (R,Z)-6-(2,3-difluorophenyl)-6,7-dihydro-5H-cyclohepta[b]pyridine (110 mg, 0.428 mmol) and NMO (110 mg, 0.941 mmol) in acetone (2 mL) and water (0.04 mL) to give a tan solution. Osmium tetroxide (0.021 mL, 1.710 μmol) (2.5 wt-% solution in 2-methyl-2-propanol) was added (the tan color instantly changed to very light yellow). The mixture was stirred at room temperature. 1 h: <5% conversion. 0.021 mL OsO4 was added. 22 h: ⅓ conversion. Another 0.021 mL OsO4 solution was added. 28 h (50 h total). Sodium bisulfate (1.2 g) was added and stirring continued for 30 min. Acetone was removed in vacuo and the residue was extracted with ethyl acetate three times. The combined organic layers were washed with brine, dried and concentrated to an off-white solid. FCC (a few drops of methanol helped to completely dissolve the solids in methylene chloride) up to 10% methanol/methylene chloride afforded two products: a less polar, likely the desired trans product (61 mg, 49%) and a more polar cis product (47.1 mg, 38%) as white solids. MS(ESI)[M+H+]=258.16, 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.46 (d, J=5.04 Hz, 1H) 7.50 (dd, J=7.55, 1.26 Hz, 1H) 7.22 (dd, J=7.43, 4.91 Hz, 1H) 7.01-7.10 (m, 3H) 5.04 (s, 1H) 4.43 (br. s., 1H) 3.35 (dd, J=11.33, 3.53 Hz, 1H) 3.24 (t, J=12.97 Hz, 1H) 2.86 (d, J=14.35 Hz, 1H) 2.30-2.44 (m, 2H); 19F NMR (376 MHz, CHLOROFORM-d) δ ppm −138.07-−137.86 (m, 1F) −142.98-−142.63 (m, 1F).

Provenance & Evidence