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

HRID 1625343Notes

Reaction equation

HRID 1625343 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 sulphate 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 sulphate was added
  5. customThe solids were removed by filtration
  6. washbeing well washed with ethyl acetate

Sources & evidence

ORD record
ord-799c65232da24a6a9b9c5eac47a228fe
Source dataset
uspto-grants-2014_07
Patent number
US08779132B2

Reaction notes

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