Nitric Acid → 4-bromo-5-fluoro-2-methyl-7-nitro-2,3-dihydro-1H-isoindol-1-one

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Reaction Steps

A solution of 4-bromo-5-fluoro-2-methyl-2,3-dihydro-1H-isoindol-1-one (Compound 31F, 1.5 g, 6.1 mmol) in sulfuric acid (3.0 mL, 56 mmol) was cooled in an ice bath to 0° C. and then charged with nitric acid (2.0 mL, 43 mmol). The reaction mixture was allowed to stir overnight while gradually warming to rt. The reaction mixture was quenched by adding the mixture dropwise into a separatory funnel containing ice and then extracted with DCM (15 mL). The organic layer was washed with brine (15 mL), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to a yellow solid. The crude material was purified using a Teledyne ISCO Combiflash® Rf system using DCM/EtOAc (100:0→90:10) as eluent to afford the product compound as a yellow solid (493 mg, 28%). 1H NMR (CDCl3, 400 MHz): δ 7.60 (d, J=7.6 Hz, 1H) 4.39 (s, 2H) 3.23 (s, 3H). MS (ESI): m/z=290.96 [M+H]+. UPLC: tR=1.23 min (UPLC-TOF: polar—3 min).

Provenance & Evidence