Toluene → 2-Benzyl-5-methoxy-2,3-dihydro-1H-isoindole

HRID 228390Notes

Reaction equation

HRID 228390 reaction equation
Br[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][CH3:10])=[CH:5][C:4]=1[CH2:11]Br.[OH-].[Na+].C1(C)C=CC=CC=1.[CH2:22]([NH2:29])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1.C(OCC)(=O)C>[CH2:22]([N:29]1[CH2:11][C:4]2[C:3](=[CH:8][CH:7]=[C:6]([O:9][CH3:10])[CH:5]=2)[CH2:2]1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 7504BenzylamineHCID 14798Sodium HydroxideHCID 105417861,2-Bis(bromomethyl)-4-methoxybenzene

Product 1

HCID 151678992-Benzyl-5-methoxy-2,3-dihydro-1H-isoindoleYield 71.4%

Reagents, catalysts & solvents 2

HCID 66133Benzyl triethylammonium chlorideCatalystHCID 8857Ethyl AcetateSolvent2×

Procedure

Combine in a round bottom flask 1,2-bis-bromomethyl-4-methoxy-benzene (1.0 g, 3.40 mmol), benzyltriethylammonium chloride (73.5 mg, 3.2 mmol), 50% NaOH (aq)/toluene (3.0 mL/14 mL), and then drop wise add benzylamine (0.37 mL, 3.39 mmol). Stir the reaction at room temperature for 3 hours, add to ethyl acetate, wash with water, brine, and dry over Na2SO4. After concentrating under reduced pressure, add the mixture to a 10 g SCX column, wash with MeOH, and elute with 1.0 N NH3-MeOH. Flash chromatograph using 3:1 hexanes:ethyl acetate to afford 580.0 mg, 2.42 mmol (71% yield) of the title compound as a brown oil: 1H NMR (500 MHz, CDCl3); 3.7 (3H, s), 3.9-4.0 (6H, m), 6.7-6.8 (2H, m), 7.1 (1H, d), 7.3-7.5 (5H, m); MS m/z 238 (M−1).

Workup

  1. customthe reaction at room temperature for 3 hours
  2. washwash with water, brine
  3. dry with materialdry over Na2SO4
  4. concentrationAfter concentrating under reduced pressure
  5. additionadd the mixture to a 10 g SCX column
  6. washwash with MeOH
  7. washelute with 1.0 N NH3-MeOH

Sources & evidence

ORD record
ord-e1e10dc5ae6943b3bb21ad7081426df8
Source dataset
uspto-grants-2009_07
Patent number
US07560463B2

Reaction notes

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