Benzylamine → 2-Benzyl-4-bromo-7-fluoro-2,3-dihydro-1H-isoindole

HRID 1511565Notes

Reaction equation

HRID 1511565 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[C:4]([CH2:9]Br)[C:3]=1[CH2:11]Br.C(=O)([O-])O.[K+].[CH2:18]([NH2:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>CC#N>[CH2:18]([N:25]1[CH2:11][C:3]2[C:4](=[C:5]([F:8])[CH:6]=[CH:7][C:2]=2[Br:1])[CH2:9]1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

5

Reactant 3

HCID 7504BenzylamineHCID 516893Potassium BicarbonateHCID 57431195HCID 57431195, compound

Product 1

HCID 574311962-Benzyl-4-bromo-7-fluoro-2,3-dihydro-1H-isoindoleYield 46.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
25 °C

Procedure

To a mixture of 1-bromo-2,3-bis(bromomethyl)-4-fluorobenzene (7.59 g, 21.0 mmol) and potassium hydrogen carbonate (5.26 g, 52.6 mmol) in 800 mL CH3CN was added benzylamine (2.25 g, 21.0 mmol). The resulting suspension was refluxed for 8 h then stirred at 25° C. for 18 h. The mixture was filtered, and the residue was purified by column chromatography on silica gel (gradient elution, 10 to 60% DCM in hexanes) and concentrated to give 2-benzyl-4-bromo-7-fluoroisoindoline (3.00 g, 46% yield) as colorless oil. LRMS (ESI) m/z 306.3 [(M+H)+; calcd for C15H14NBrF: 306.2].

Workup

  1. temperatureThe resulting suspension was refluxed for 8 h
  2. filtrationThe mixture was filtered
  3. customthe residue was purified by column chromatography on silica gel (gradient elution, 10 to 60% DCM in hexanes)
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-4c970d0a40d74b97a370c859a0fc51f4
Source dataset
uspto-grants-2012_07
Patent number
US08216999B2

Reaction notes

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