Tetrahydrofuran → 2-(4-methoxy-benzyl)-4-[2-(2-methoxy-ethoxy)-ethoxy]-2,3-dihydro-1H-isoindole

HRID 2060129Notes

Reaction equation

HRID 2060129 reaction equation
[CH3:1][O:2][C:3]1[CH:28]=[CH:27][C:6]([CH2:7][N:8]2[C:16](=O)[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][C:14]=3[O:18][CH2:19][CH2:20][O:21][CH2:22][CH2:23][O:24][CH3:25])[C:9]2=O)=[CH:5][CH:4]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].C1COCC1>>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]2[CH2:16][C:15]3[C:10](=[CH:11][CH:12]=[CH:13][C:14]=3[O:18][CH2:19][CH2:20][O:21][CH2:22][CH2:23][O:24][CH3:25])[CH2:9]2)=[CH:27][CH:28]=1

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 21226445Aluminium lithium hydrideHCID 592631332-(4-Methoxy-benzyl)-4-[2-(2-methoxy-ethoxy)-ethoxy]-isoindole-1,3-dione

Product 1

HCID 592631462-(4-methoxy-benzyl)-4-[2-(2-methoxy-ethoxy)-ethoxy]-2,3-dihydro-1H-isoindoleYield 98.7%

Conditions

Temperature
60 °C

Procedure

2-(4-Methoxy-benzyl)-4-[2-(2-methoxy-ethoxy)-ethoxy]-isoindole-1,3-dione (149 mg, 0.38 mmol) was treated with a 1M solution of lithium aluminium hydride in THF (5 mL, 5 mmol). The mixture was maintained at r.t. for 4 hours, 60° C. for 1 hour, then r.t. for a further 18 hours. The mixture was then cooled in ice and quenched by the dropwise addition of water (0.2 mL), 2N sodium hydroxide solution (0.4 mL) and water (0.4 mL). Magnesium sulfate was added, followed by ethyl acetate and then the mixture was stirred at r.t. for 15 minutes. The solids were removed by filtration, being well washed with ethyl acetate. Concentration of the filtrate gave a residue which was absorbed onto an SCX cartridge and washed with 5% methanol/dichloromethane then eluted with 10% 1M ammonia in methanol/dichloromethane to afford the title compound (134 mg, 97%). 1H NMR (methanol-d4) 7.43-7.39 (2H, m), 7.27 (1H, t), 6.99-6.96 (2H, m), 6.90 (1H, d), 6.88 (1H, d), 4.33 (2H, s), 4.28 (2H, s), 4.23 (2H, s), 4.18-4.15 (2H, m), 3.85-3.79 (5H, m), 3.67-3.64 (2H, m), 3.54-3.51 (2H, m), 3.33 (3H, s). MS: [M+H]+ 358.

Workup

  1. temperatureThe mixture was then cooled in ice
  2. customquenched by the dropwise addition of water (0.2 mL), 2N sodium hydroxide solution (0.4 mL) and water (0.4 mL)
  3. additionMagnesium sulfate was added
  4. customThe solids were removed by filtration
  5. washbeing well washed with ethyl acetate
  6. customConcentration of the filtrate gave a residue which
  7. customwas absorbed onto an SCX cartridge
  8. washwashed with 5% methanol/dichloromethane
  9. washthen eluted with 10% 1M ammonia in methanol/dichloromethane

Sources & evidence

ORD record
ord-593816c732ad43e3bee0ee237d0393fb
Source dataset
uspto-grants-2012_10
Patent number
US08277807B2

Reaction notes

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