Sodium hydride → 4-[2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)ethoxy]benzaldehyde

HRID 2260699Notes

Reaction equation

HRID 2260699 reaction equation
[H-].[Na+].[OH:3][CH2:4][CH2:5][N:6]1[C:10](=[O:11])[C:9]2=[CH:12][CH:13]=[CH:14][CH:15]=[C:8]2[C:7]1=[O:16].F[C:18]1[CH:25]=[CH:24][C:21]([CH:22]=[O:23])=[CH:20][CH:19]=1>CN(C)C=O>[C:10]1(=[O:11])[N:6]([CH2:5][CH2:4][O:3][C:18]2[CH:25]=[CH:24][C:21]([CH:22]=[O:23])=[CH:20][CH:19]=2)[C:7](=[O:16])[C:8]2=[CH:15][CH:14]=[CH:13][CH:12]=[C:9]12

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 680234-FluorobenzaldehydeHCID 77499N-(2-Hydroxyethyl)phthalimide

Product 1

HCID 128106414-[2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)ethoxy]benzaldehyde

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (60% dispersion in oil, 2 g) was added portionwise to a solution of N-(2-hydroxyethyl)phthalimide (9.6 g) in dry dimethylformamide (70 ml) at room temperature under a nitrogen atmosphere. The mixture was stirred at room temperature for 1 hour prior to the addition of 4-fluorobenzaldehyde (6.2 g, 5.3 ml), and the mixture then heated at 80° C. for 15 hours. The solvent was evaporated and the residue dissolved in water (100 ml) and extracted with ethyl acetate (2×100 ml). The combined ethyl acetate layers were washed with water (2×100 ml), brine (100 ml), dried (MgSO4) and evaporated to yield an oil. The oil was triturated with hexane, and the residue chromatographed on silica gel with 1.5% methanol in dichloromethane to afford the title compound mp 138° C.

Workup

  1. temperaturethe mixture then heated at 80° C. for 15 hours
  2. customThe solvent was evaporated
  3. dissolutionthe residue dissolved in water (100 ml)
  4. extractionextracted with ethyl acetate (2×100 ml)
  5. washThe combined ethyl acetate layers were washed with water (2×100 ml), brine (100 ml)
  6. dry with materialdried (MgSO4)
  7. customevaporated
  8. customto yield an oil
  9. customThe oil was triturated with hexane
  10. customthe residue chromatographed on silica gel with 1.5% methanol in dichloromethane

Sources & evidence

ORD record
ord-2507e38daf9c4197b7a0bd478082b058
Source dataset
uspto-grants-1995_12
Patent number
US05478850

Reaction notes

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