Water → 2-[5-(4-Fluoro-benzyloxy)-1,3-dioxo-1,3-dihydro-isoindol-2-yl]-acetamide

HRID 431582Notes

Reaction equation

HRID 431582 reaction equation
[F:1][C:2]1[CH:20]=[CH:19][C:5]([CH2:6][O:7][C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)[C:13](=[O:17])[NH:12][C:11]3=[O:18])=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:24][C:25]([NH2:27])=[O:26].O>O1CCCC1>[F:1][C:2]1[CH:20]=[CH:19][C:5]([CH2:6][O:7][C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)[C:13](=[O:17])[N:12]([CH2:24][C:25]([NH2:27])=[O:26])[C:11]3=[O:18])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 696322-BromoacetamideHCID 223970815-(4-Fluoro-benzyloxy)-isoindole-1,3-dione

Product 1

HCID 101257982-[5-(4-Fluoro-benzyloxy)-1,3-dioxo-1,3-dihydro-isoindol-2-yl]-acetamideYield 65%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 5-(4-fluoro-benzyloxy)-isoindole-1,3-dione (100 mg, 0.37 mmol), sodium hydride (55% in mineral oil, 18 mg, 0.42 mmol) and 2-bromoacetamide (61 mg, 0.44 mmol) in dry tetrahydrofuran (5 mL) at 0° C. was stirred at room temperature for 3 h and then heated at 50° C. for 1 h. After cooling to 0° C., water (2 mL) was added and the product extracted with ethyl acetate. The organic extracts were then washed with brine and dried over sodium sulfate. Filtration and evaporation gave a residue which was purified by chromatography (SiO2, heptane-CH2Cl2 2:3 then CH2Cl2— 2N NH3—MeOH 99:1: to 4:1) to afford the title compound (78 mg, 65%) as a white solid. MS: m/e=329.3 (M+H+).

Workup

  1. temperatureheated at 50° C. for 1 h
  2. temperatureAfter cooling to 0° C.
  3. extractionthe product extracted with ethyl acetate
  4. washThe organic extracts were then washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationFiltration and evaporation
  7. customgave a residue which
  8. customwas purified by chromatography (SiO2, heptane-CH2Cl2 2:3

Sources & evidence

ORD record
ord-2bf4cc49c1a340f6bb33e1f15a8d995e
Source dataset
uspto-grants-2003_12
Patent number
US06660736B2

Reaction notes

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