Ammonia → 5-Bromo-7-fluoro-2,3-dihydro-1H-isoindol-1-one

HRID 605979Notes

Reaction equation

HRID 605979 reaction equation
C[O:2][C:3](=O)[C:4]1[C:9]([CH2:10][N+:11]([O-])=O)=[CH:8][C:7]([Br:14])=[CH:6][C:5]=1[F:15].C([O-])=O.[NH4+].N>CO.C(Cl)Cl.[Zn]>[Br:14][C:7]1[CH:8]=[C:9]2[C:4](=[C:5]([F:15])[CH:6]=1)[C:3](=[O:2])[NH:11][CH2:10]2

Participants

7

Reactant 3

HCID 222AmmoniaHCID 2723923Ammonium formateHCID 57590089HCID 57590089, compound

Product 1

HCID 497580245-Bromo-7-fluoro-2,3-dihydro-1H-isoindol-1-one

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent

Procedure

Crude 4-bromo-2-fluoro-6-(nitromethyl)benzoic acid methyl ester from the previous step is dissolved in MeOH (100 mL). To this clear orange solution is added Zinc dust (3.35 g, 51.3 mmol, 3 equiv.) followed by ammonium formate (3.23 g, 51.3 mmol, 3 equiv.) which results in an exothermic reaction. After 0.3 h, 7M NH3 in MeOH (50 mL) is added and the mixture is stirred overnight at room temperature. The resulting mixture is filtered through celite, and the yellow filtrate is adsorbed on silica and roughly cleaned by LC using 94/6 DCM/MeOH 7M NH3. Removal of the solvent affords a tan solid that is redissolved in DCM, washed with 10% NaOH, and concentrated under reduced pressure to leave a white solid, which is triturated further with small amounts of DCM to afford the title compound. LCMS: Rt 0.96 min (100%) m/z 230/232 (M+H)+.

Workup

  1. customresults in an exothermic reaction
  2. filtrationThe resulting mixture is filtered through celite
  3. customRemoval of the solvent
  4. customaffords a tan solid
  5. washwashed with 10% NaOH
  6. concentrationconcentrated under reduced pressure
  7. customto leave a white solid, which
  8. customis triturated further with small amounts of DCM

Sources & evidence

ORD record
ord-a2afb11f8b494ac3a0e4eb8c8f4d1d2b
Source dataset
uspto-grants-2011_03
Patent number
US07915256B2

Reaction notes

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