Dimethylformamide → tert-butyl [5-chloro-1'-[(5-methyl-3-phenylisoxazol-4-yl)methyl]-2,2'-dioxospiro[indole-3,3'-pyrrolidin]-1(2H)-yl]acetate

HRID 883659Notes

Reaction equation

HRID 883659 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]3([CH2:14][C:13](=O)[NH:12][CH2:11]3)[C:9](=[O:16])[N:8]([CH2:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C:5]2=[CH:6][CH:7]=1.[H-].[Na+].Br[CH2:28][C:29]1[C:30]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)=[N:31][O:32][C:33]=1[CH3:34].CN(C=[O:45])C>C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]3([CH2:14][CH2:13][N:12]([CH2:28][C:29]4[C:30]([C:35]5[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=5)=[N:31][O:32][C:33]=4[CH3:34])[C:11]3=[O:45])[C:9](=[O:16])[N:8]([CH2:17][C:18]([O:20][C:21]([CH3:24])([CH3:22])[CH3:23])=[O:19])[C:5]2=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 27761474-(Bromomethyl)-5-methyl-3-phenylisoxazoleHCID 24827314tert-butyl (5-chloro-2,5'-dioxospiro[indole-3,3'-pyrrolidin]-1(2H) yl)acetate

Product 1

HCID 24827318tert-butyl [5-chloro-1'-[(5-methyl-3-phenylisoxazol-4-yl)methyl]-2,2'-dioxospiro[indole-3,3'-pyrrolidin]-1(2H)-yl]acetateYield 58%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A suspension of tert-butyl (5-chloro-2,5′-dioxospiro[indole-3,3′-pyrrolidin]-1(2H)-yl)acetate, intermediate 41 (100 mg; 0.29 mmol) in dry DMF (5 ml) was treated with sodium hydride pract. (14.8 mg; 0.37 mmol). After stirring for 20 minutes 4-(bromomethyl)-5-methyl-3-phenylisoxazole (86.24 mg; 0.34 mmol) was added. After stirring for 1 h the solvent was evaporated to give a residue, which was dissolved in ethyl acetate. The organic phase was washed with brine, dried (MgSO4) and removed in vacuo, to give a solid residue which was purified by chromatography (silica), eluting with cyclohexane containing increasing amounts of ethyl acetate (30 to 50%), to give the title compound in 58% yield (HPLC purity 99%). MS (ESI+): 522.4; MS (ESI−): 520.2

Workup

  1. additionwas added
  2. customwas evaporated
  3. customto give a residue, which
  4. washThe organic phase was washed with brine
  5. dry with materialdried (MgSO4)
  6. customremoved in vacuo
  7. customto give a solid residue which
  8. customwas purified by chromatography (silica)
  9. washeluting with cyclohexane containing
  10. temperatureincreasing amounts of ethyl acetate (30 to 50%)

Sources & evidence

ORD record
ord-b8eef6fe21ef4c2da7f009b6921de091
Source dataset
uspto-grants-2012_08
Patent number
US08236963B2

Reaction notes

Loading…