Sodium hydride → [3-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-pyrazol-1-yl]-acetic acid tert-butyl ester

HRID 1951220Notes

Reaction equation

HRID 1951220 reaction equation
[H-].[Na+].[NH:3]1[CH:7]=[CH:6][C:5]([N:8]2[C:16](=[O:17])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]2=[O:18])=[N:4]1.Br[CH2:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22]>CN(C=O)C>[C:24]([O:23][C:21](=[O:22])[CH2:20][N:3]1[CH:7]=[CH:6][C:5]([N:8]2[C:16](=[O:17])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]2=[O:18])=[N:4]1)([CH3:27])([CH3:26])[CH3:25]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 79177tert-Butyl bromoacetateHCID 178514958HCID 178514958, compound

Product 1

HCID 67201871[3-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-pyrazol-1-yl]-acetic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (60% in oil, 0.538 g, 13.4 mmol) is added to a stirred solution of 2-(1H-pyrazol-3-yl)-isoindole-1,3-dione (2.39 g, 11.2 mmol) in dry DMF (25 ml) at room temperature. After 10 minutes tert-butyl bromoacetate (1.81 ml, 11.2 mmol) is added and the reaction is stirred for 18 hours. The reaction is quenched with water (1 ml), ethyl acetate (150 ml) is added and the organic phase is washed with water (3×100 ml) followed by brine (1×100 ml). The solvent is removed and the product is purified by chromatography on silica (gradient elution: ethyl acetate—hexane) to give the titled compound.

Workup

  1. customThe reaction is quenched with water (1 ml), ethyl acetate (150 ml)
  2. additionis added
  3. washthe organic phase is washed with water (3×100 ml)
  4. customThe solvent is removed
  5. customthe product is purified by chromatography on silica (gradient elution: ethyl acetate—hexane)

Sources & evidence

ORD record
ord-9f4a8664df914aeab38839ce25f212d6
Source dataset
uspto-grants-2013_03
Patent number
US08404684B2

Reaction notes

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