Methyl iodide → 5-Bromo-2-(4-methoxybenzyl)-3,3-dimethylisoindolin-1-one

HRID 605982Notes

Reaction equation

HRID 605982 reaction equation
[H-].[Na+].[I-].[Br:4][C:5]1C=[C:7]2[C:11](=[CH:12][CH:13]=1)[C:10](=O)NC2.[CH3:15][O:16][C:17]1[CH:24]=[CH:23][C:20]([CH2:21]Br)=[CH:19][CH:18]=1.IC.[NH4+:27].[Cl-].[CH2:29]1[CH2:33][O:32][CH2:31][CH2:30]1>CN(C=O)C.C(OCC)(=O)C>[Br:4][C:5]1[CH:13]=[C:12]2[C:29](=[CH:30][CH:31]=1)[C:33](=[O:32])[N:27]([CH2:21][C:20]1[CH:23]=[CH:24][C:17]([O:16][CH3:15])=[CH:18][CH:19]=1)[C:11]2([CH3:7])[CH3:10]

Participants

10

Reactant 7

HCID 6328Methyl iodideHCID 8028Tetrahydrofuran2×HCID 24758Sodium hydride2×HCID 25517Ammonium ChlorideHCID 30165Iodide IonHCID 1650214-Methoxybenzyl bromideHCID 226071195-bromo-2,3-dihydro-1H-isoindol-1-one

Product 1

HCID 575899515-Bromo-2-(4-methoxybenzyl)-3,3-dimethylisoindolin-1-one

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A suspension of sodium hydride (130 mg, 60% dispersion in mineral oil, 3.2 mmol) and tetra-nbutylammonium iodide (243 mg, 0.68 mmol) in THF (20 mL) is stirred at rt and a solution of 5-bromo-2,3-dihydroisoindol-1-one (675 mg, 3.2 mmol) in THF (20 mL) and DMF (4 mL) is added. After 75 min 4-methoxybenzyl bromide (460 μL, 3.2 mmol) is added and stirring is continued for 4 h. Sodium hydride (635 mg, 60% dispersion in mineral oil, 15.9 mmol) is then added and stirring is continued for 30 min before iodomethane (1.19 mL, 19 mmol) is added and the mixture heated to 70° C. for 30 min. After cooling, NH4Cl (sat. aq.) is added and the mixture is diluted with ethyl acetate (120 mL). The layers are separated, the organic phase is dried over MgSO4 and the solvents removed under reduced pressure. The residue is purified by silica chromatography, eluting with 5% to 10% ethyl acetate in petroleum ether to afford the title compound as a yellow oil (640 mg, 1.78 mmol).

Workup

  1. stirringstirring
  2. stirringstirring
  3. additionis added
  4. temperaturethe mixture heated to 70° C. for 30 min
  5. temperatureAfter cooling
  6. customThe layers are separated
  7. dry with materialthe organic phase is dried over MgSO4
  8. customthe solvents removed under reduced pressure
  9. customThe residue is purified by silica chromatography
  10. washeluting with 5% to 10% ethyl acetate in petroleum ether

Sources & evidence

ORD record
ord-11b18b600d6643afacfeaa39dae22cc8
Source dataset
uspto-grants-2011_03
Patent number
US07915256B2

Reaction notes

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