Potassium Carbonate → (1R,2S)-2-(4-chlorophenyl)-1'-(1-trityl-1 H-imidazol-4-yl)spiro[cyclopropane-1,3'-indolin]-2'-one

HRID 1805331Notes

Reaction equation

HRID 1805331 reaction equation
I[C:2]1[N:3]=[CH:4][N:5]([C:7]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=1.[Cl:26][C:27]1[CH:32]=[CH:31][C:30]([CH:33]2[C:35]3([C:43]4[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=4)[NH:37][C:36]3=[O:44])[CH2:34]2)=[CH:29][CH:28]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)CCN>C(#N)C.[Cu]I>[Cl:26][C:27]1[CH:28]=[CH:29][C:30]([C@H:33]2[C@@:35]3([C:43]4[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=4)[N:37]([C:2]4[N:3]=[CH:4][N:5]([C:7]([C:8]5[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=5)([C:20]5[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=5)[C:14]5[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=5)[CH:6]=4)[C:36]3=[O:44])[CH2:34]2)=[CH:31][CH:32]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 66053N,N-DimethylethylenediamineHCID 6182524-Iodo-1-tritylimidazoleHCID 672320902-(4-Chlorophenyl)spiro[cyclopropane-1,3'-indolin]-2'-one

Product 1

HCID 58305304(1R,2S)-2-(4-chlorophenyl)-1'-(1-trityl-1 H-imidazol-4-yl)spiro[cyclopropane-1,3'-indolin]-2'-one

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
40 °C

Procedure

4-Iodo-1-trityl-1 H-imidazole (210 mg, 0.48 mmol) was added to a suspension of racemic (1S,2R)-2-(4-chlorophenyl)spiro[cyclopropane-1,3′-indolin]-2′-one (107 mg, 0.4 mmol) in acetonitrile (2 mL) under a nitrogen atmosphere. A steady stream of nitrogen was bubbled through the suspension as it was heated to 40° C. over 15 minutes. Potassium carbonate (110 mg, 0.8 mmol), copper (I) iodide (12 mg, 15 mol %), and N,N-dimethylethylenediamine (0.12 mmol, 30 mol %) were added and the reaction mixture was heated to 80° C. and kept for 21 hours under nitrogen atmosphere. The mixture was cooled to room temperature, filtered and concentrated to give the title product. The residue was purified by flash column chromatography (gradient elution, 5-10% ethyl acetate in petroleum ether) to give racemic trans-2-(4-chlorophenyl)-1′-(1 H-imidazol-4-trityl)spiro[cyclopropane-1,3′-indolin]-2′-one (157 mg, 68%). LC/MS m/e calcd. for C38H28ClN3O: 577, observed (M+H)+: 578.2 MS calcd. for C38H28ClN3O 578, obsd. (ESI+) [(M+H)+] 579.3.

Workup

  1. customA steady stream of nitrogen was bubbled through the suspension as it
  2. temperaturethe reaction mixture was heated to 80° C.
  3. temperatureThe mixture was cooled to room temperature
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-ff98a91a0b8944029b8fb81e066379bc
Source dataset
uspto-grants-2013_01
Patent number
US08354443B2

Reaction notes

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