Nitric Acid → 4-bromo-5-fluoro-2-methyl-7-nitro-2,3-dihydro-1H-isoindol-1-one
Reaction equation
[Br:1][C:2]1[C:10]([F:11])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][N:5]([CH3:13])[C:6]2=[O:12].S(=O)(=O)(O)O.[N+:19]([O-])([OH:21])=[O:20]>>[Br:1][C:2]1[C:10]([F:11])=[CH:9][C:8]([N+:19]([O-:21])=[O:20])=[C:7]2[C:3]=1[CH2:4][N:5]([CH3:13])[C:6]2=[O:12]Participants
Procedure
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).
Workup
- customThe reaction mixture was quenched
- additionby adding the mixture dropwise into a separatory funnel
- additioncontaining ice
- extractionextracted with DCM (15 mL)
- washThe organic layer was washed with brine (15 mL)
- dry with materialdried over anhydrous Na2SO4
- filtrationfiltered
- concentrationconcentrated under reduced pressure to a yellow solid
- customThe crude material was purified
Sources & evidence
- ORD record
- ord-cc540f552d644dcfb2ee6e659b30f3dc
- Source dataset
- uspto-grants-2015_09
- Patent number
- US09133224B2
Reaction notes
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