Tetrahydrofuran → 2-(2,4-Dimethoxy-benzyl)-4-(2-dimethylamino-ethoxy)-2,3-dihydro-1H-isoindole

HRID 2412180Notes

Reaction equation

HRID 2412180 reaction equation
[CH3:1][O:2][C:3]1[CH:26]=[C:25]([O:27][CH3:28])[CH:24]=[CH:23][C:4]=1[CH2:5][N:6]1[C:14](=O)[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][C:12]=2[O:16][CH2:17][CH2:18][N:19]([CH3:21])[CH3:20])[C:7]1=O.[H-].[Al+3].[Li+].[H-].[H-].[H-].C1COCC1>>[CH3:1][O:2][C:3]1[CH:26]=[C:25]([O:27][CH3:28])[CH:24]=[CH:23][C:4]=1[CH2:5][N:6]1[CH2:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][C:12]=2[O:16][CH2:17][CH2:18][N:19]([CH3:21])[CH3:20])[CH2:7]1

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 21226445Aluminium lithium hydride2×HCID 592631232-(2,4-Dimethoxy-benzyl)-4-(2-dimethylamino-ethoxy)-isoindole-1,3-dione

Product 1

HCID 592631072-(2,4-Dimethoxy-benzyl)-4-(2-dimethylamino-ethoxy)-2,3-dihydro-1H-isoindoleYield 103.6%

Procedure

2-(2,4-Dimethoxy-benzyl)-4-(2-dimethylamino-ethoxy)-isoindole-1,3-dione (201 mg, 0.52 mmol) was treated with a 1M solution of lithium aluminium hydride in THF (5 mL, 5 mmol). After 7.5 hours at r.t. a further portion of lithium aluminium hydride solution (5 mL, 5 mmol) was added and the mixture maintained for further 18 hours. The mixture was then cooled in ice and quenched by the dropwise addition of water (0.4 mL), 2N sodium hydroxide solution (0.8 mL) and water (0.8 mL). Magnesium sulfate was added, followed by ethyl acetate and then the mixture was stirred at r.t. for 1 hour. The solids were removed by filtration, being well washed with ethyl acetate. Concentration of the filtrate gave the title compound (192 mg, 103%) as a brown oil which was carried forward without further purification. 1H NMR (methanol-d4) 7.24 (1H, d), 7.16 (1H, t), 6.82-6.78 (2H, m), 6.55 (1H, d), 6.51 (1H, dd), 4.12 (2H, t), 3.92 (4H, s), 3.86 (2H, s), 3.82 (3H, s), 3.80 (3H, s), 2.76 (2H, t), 2.33 (6H, s). MS: [M+H]+ 357.

Workup

  1. temperaturethe mixture maintained for further 18 hours
  2. temperatureThe mixture was then cooled in ice
  3. customquenched by the dropwise addition of water (0.4 mL), 2N sodium hydroxide solution (0.8 mL) and water (0.8 mL)
  4. additionMagnesium sulfate was added
  5. customThe solids were removed by filtration
  6. washbeing well washed with ethyl acetate

Sources & evidence

ORD record
ord-8fe3003047ca4c4d9c14db56287698d7
Source dataset
uspto-grants-2014_08
Patent number
US08816087B2

Reaction notes

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