Cesium carbonate → tert-butyl 5-(2-oxopyrrolidin-1-yl)-1H-indole-1-carboxylate

HRID 1467977

Reaction equation

HRID 1467977 reaction equation
I[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH:6]=[CH:5]2.[NH:18]1[CH2:22][CH2:21][CH2:20][C:19]1=[O:23].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C(Cl)(Cl)Cl.[Pd].[Pd]>[O:23]=[C:19]1[CH2:20][CH2:21][CH2:22][N:18]1[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH:6]=[CH:5]2

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 120252-PyrrolidoneHCID 161259585-Iodo-1H-indole, N-BOC protected

Product 1

HCID 67616327tert-butyl 5-(2-oxopyrrolidin-1-yl)-1H-indole-1-carboxylateYield 61.9%

Reagents, catalysts & solvents 2

HCID 11029508Palladium, tris[mu-[(1,2-eta:4,5-eta)-(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one]]di-, compd. with trichloromethane (1:1)CatalystHCID 312751,4-DioxaneSolvent

Procedure

To a stirred mixture of tert-butyl 5-iodo-1H-indole-1-carboxylate (1.5 g, 4.3 mmol), Xant Phos (0.25 g, 0.43 mmol) and 2-pyrrolidinone (0.74 g, 8.7 mmol) in anhydrous dioxane (15 mL), cesium carbonate (2.8 g, 8.7 mmol) was added and the contents were stirred for 5 minutes. Tris(dibenzylideneacetone)-dipalladium (0)chloroform adduct (0.452 g, 0.437 mmol) was added and the reaction mixture was stirred at 110-115° C. for 6 h. The reaction mixture was cooled to room temperature and filtered over celite and filtrate was extracted with ethyl acetate. The organic layer was concentrated in vacuo and the residue was purified by flash column chromatography to yield tert-butyl 5-(2-oxopyrrolidin-1-yl)-1H-indole-1-carboxylate (0.80 g, 61%); MS: 301 (M+1).

Workup

  1. additionwas added
  2. stirringthe reaction mixture was stirred at 110-115° C. for 6 h
  3. filtrationfiltered over celite and filtrate
  4. extractionwas extracted with ethyl acetate
  5. concentrationThe organic layer was concentrated in vacuo
  6. customthe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-c76cba1980ce4fd093d34909079f1882
Source dataset
uspto-grants-2015_04
Patent number
US09000175B2

Linked notes

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