Benzoyl Peroxide → Methyl 2-(4-methoxybenzyl)isoindoline-5-carboxylate

HRID 508570Notes

Reaction equation

HRID 508570 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[CH3:12])[C:5]([O:7][CH3:8])=[O:6].BrN1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.C(N(CC)CC)C.[CH3:46][O:47][C:48]1[CH:55]=[CH:54][C:51]([CH2:52][NH2:53])=[CH:50][CH:49]=1>C(Cl)(Cl)(Cl)Cl.C1COCC1>[CH3:46][O:47][C:48]1[CH:55]=[CH:54][C:51]([CH2:52][N:53]2[CH2:1][C:2]3[C:11](=[CH:10][CH:9]=[C:4]([C:5]([O:7][CH3:8])=[O:6])[CH:3]=3)[CH2:12]2)=[CH:50][CH:49]=1

Participants

8

Reactant 5

HCID 7187Benzoyl PeroxideHCID 8471TriethylamineHCID 67184N-bromobutanimideHCID 754524-MethoxybenzylamineHCID 520902Methyl 3,4-dimethylbenzoate

Product 1

HCID 58147238Methyl 2-(4-methoxybenzyl)isoindoline-5-carboxylateYield 49%

Reagents, catalysts & solvents 2

HCID 5943Carbon TetrachlorideSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A mixture of methyl 3,4-dimethylbenzoate (1.334 g, 8.13 mmol), N-bromosuccinimide (3.173 g, 17.83 mmol) and benzoyl peroxide (0.143 g, 0.592 mmol) in carbon tetrachloride (5 mL) was heated at reflux for 1.5 hours. Upon cooling to room temperature, the solids present were removed by vacuum filtration and the resulting solution concentrated in vacuo. The residue obtained was re-dissolved in THF (30 mL). To the solution was added triethylamine (2.265 mL, 16.25 mmol) and a solution of 4-methoxy benzylamine (1.05 mL, 8.13 mmol) in THF (20 mL). The resulting reaction mixture was stirred overnight at room temperature. The precipitate was removed via filtration and the solution obtained was concentrated in vacuo. The residue obtained was purified via flash chromatography (15-30% EtOAc/hexane) to afford a light yellow oil (1.185 g). LCMS: (FA) ES+ 298; 1H NMR (CDCl3, 400 MHz) 7.89 (dd, J=7.8, 1.5 Hz, 1H), 7.84 (s, 1H), 8.74 (d, J=8.7 Hz, 2H), 7.313 (d, J=8.7 Hz 2H), 7.22 (d, J=7.2 Hz, 2H), 6.89 (d, J=8.7 Hz, 2H), 3.93 (s, 4H), 3.89 (s, 3H), 3.85 (s, 2H), 3.82 (s, 3H).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 1.5 hours
  3. customthe solids present were removed by vacuum filtration
  4. concentrationthe resulting solution concentrated in vacuo
  5. customThe residue obtained
  6. customThe resulting reaction mixture
  7. customThe precipitate was removed via filtration
  8. customthe solution obtained
  9. concentrationwas concentrated in vacuo
  10. customThe residue obtained
  11. customwas purified via flash chromatography (15-30% EtOAc/hexane)

Sources & evidence

ORD record
ord-ce547ad2ccab415eb87838eb9c7a6cec
Source dataset
uspto-grants-2015_08
Patent number
US09096518B2

Reaction notes

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