Acetic Acid → 4-(2-methoxy-4-(trifluoromethyl)phenyl)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonyl chloride

Participants

Reaction Conditions

Reaction Steps

Dissolve 7-amino-4-(2-methoxy-4-(trifluoromethyl)phenyl)-2H-benzo[b][1,4]oxazin-3(4H)-one (1.4 g, 4.14 mmol) in hydrogen chloride (2.096 ml, 24.83 mmol) and acetic acid (4.74 ml, 83 mmol) in a 250 mL rbf and cooled to 0° C. Added sodium nitrite (0.314 g, 4.55 mmol) dissolved in water (0.746 ml, 41.4 mmol) and let stir at 0° C. for 30 min until azide formation by LCMS. Then bubbled sulfur dioxide (0.265 g, 4.14 mmol) gas into solution for 5 minutes and added copper(I) chloride (0.205 g, 2.069 mmol), then bubbled more sulfur dioxide into the solution for 5 minutes. Let stir at rt for 3 hr until reaction was complete by LCMS. Quenched reaction over ice, added EtOAc (100 mL) and brine (100 mL) and extracted 3 times with EtOAc (3×100 mL). Dried organics over Na2SO4 and concentrated via rotary evaporation. Purified 4-(2-methoxy-4-(trifluoromethyl)phenyl)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonyl chloride (1.041 g, 2.468 mmol, 59.6% yield) via MPLC with a gradient Hex:EtOAc column (0-100%) which was isolated as an off-white solid.

Provenance & Evidence