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

HRID 2279802Notes

Reaction equation

HRID 2279802 reaction equation
[Br:1][C:2]1[C:10]([F:11])=[CH:9][C:8]([N+:12]([O-])=O)=[C:7]2[C:3]=1[CH2:4][N:5]([CH3:16])[C:6]2=[O:15].Cl.O>CCO.[Fe]>[NH2:12][C:8]1[CH:9]=[C:10]([F:11])[C:2]([Br:1])=[C:3]2[C:7]=1[C:6](=[O:15])[N:5]([CH3:16])[CH2:4]2

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 962WaterHCID 678118774-bromo-5-fluoro-2-methyl-7-nitro-2,3-dihydro-1H-isoindol-1-one2×

Product 1

HCID 678138277-amino-4-bromo-5-fluoro-2-methyl-2,3-dihydro-1H-isoindol-1-oneYield 50%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 702EthanolSolvent

Procedure

A suspension of 4-bromo-5-fluoro-2-methyl-7-nitro-2,3-dihydro-1H-isoindol-1-one (Compound 31E, 490 mg, 1.70 mmol) in EtOH (10.0 mL) was charged with iron powder (473 mg, 8.48 mmol) and then heated to reflux. After 10 min of reflux, the reaction mixture was charged with 1 M of HCl in H2O (2.03 mL, 2.03 mmol) and stirred at reflux for 10 min. The reaction mixture was filtered through a pad of celite. The filtrate was concentrated under reduced pressure. The residue was quenched with NaHCO3 (10 mL) and extracted with DCM (15 mL). The organic layer was washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure to an orange solid. The crude material was purified using a Teledyne ISCO Combiflash® Rf system using DCM/MeOH (100:0→95:5) as eluent. The fractions containing product were combined and then concentrated under reduced pressure to yield a bright yellow solid (218 mg, 50%). 1H NMR (CDCl3, 400 MHz): δ 6.38 (d, J=10.9 Hz, 1H) 5.29 (br. s., 2H) 4.22 (s, 2H) 3.14 (s, 3H). MS (ESI): m/z=260.99 [M+H]+. UPLC: tR=1.26 min (UPLC-TOF: polar—3 min).

Workup

  1. temperatureheated to reflux
  2. temperatureAfter 10 min of reflux
  3. temperatureat reflux for 10 min
  4. filtrationThe reaction mixture was filtered through a pad of celite
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customThe residue was quenched with NaHCO3 (10 mL)
  7. extractionextracted with DCM (15 mL)
  8. washThe organic layer was washed with brine
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure to an orange solid
  12. customThe crude material was purified
  13. additionThe fractions containing product
  14. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a3eba1c32ec14f92b94de46548dfd4fb
Source dataset
uspto-grants-2015_09
Patent number
US09133224B2

Reaction notes

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