Hydrochloric Acid → 1-(4-bromo-2-methoxyphenyl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide

Participants

Reaction Steps

A solution of 3-aminoisoxazole (0.664 ml, 8.98 mmol) and racemic perfluorophenyl 1-(4-bromo-2-methoxyphenyl)-2-oxo-1,2-dihydroquinoline-6-sulfonate (4.705 g, 8.16 mmol) in 100 mL THF, was cooled to 0° C. LHMDS 1N in THF (17.15 ml, 17.15 mmol) was added dropwise. After stirring for an hour, HCl 1N aqueous (32.7 ml, 32.7 mmol) was added, and the reaction mixture was extracted with DCM. The organics were dried over MgSO4 and concentrated. The crude residue was triturated with ether, and the resulting solid was collected and dried yielding 1-(4-bromo-2-methoxyphenyl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (3.20 g, 6.72 mmol, 82% yield). A portion of this material was resolved. Chiral separation was performed by SFC: (S,S) Whelk-O, 50% isopropanol yielding (P)-1-(4-bromo-2-methoxyphenyl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (0.150 g, 0.315 mmol, 3.86% yield) and (M)-1-(4-bromo-2-methoxyphenyl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (0.154 g, 0.323 mmol, 3.96% yield). Analytical data for both isomers is identical. m/z (ESI) 476.1 (M+H)+. 1H NMR (ACETONITRILE-d3) δ: 8.37 (d, J=1.9 Hz, 1H), 8.23 (d, J=2.3 Hz, 1H), 7.97 (d, J=9.6 Hz, 1H), 7.78 (dd, J=8.9, 2.2 Hz, 1H), 7.43 (d, J=2.1 Hz, 1H), 7.34 (dd, J=8.3, 2.1 Hz, 1H), 7.16 (d, J=8.3 Hz, 1H), 6.71-6.79 (m, 2H), 6.45 (d, J=1.8 Hz, 1H), 3.69 (s, 3H).

Provenance & Evidence