Indole-2-carboxylic acid → cis-4-[(1H-Indol-2-ylcarbonyl)amino]-5-oxo-1-phenyl-3-pyrrolidineacetic acid

HRID 1034254Notes

Reaction equation

HRID 1034254 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[C:2]1[C:10]([OH:12])=O.[NH2:13][C@H:14]1[C:18](=[O:19])[N:17]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:16][C@H:15]1[CH2:26][C:27]([O:29]CC)=[O:28]>CN(C=O)C>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[C:2]1[C:10]([NH:13][C@H:14]1[C:18](=[O:19])[N:17]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:16][C@H:15]1[CH2:26][C:27]([OH:29])=[O:28])=[O:12]

Participants

4

Reactant 2

HCID 72899Indole-2-carboxylic acidHCID 67795246Ethyl cis-4-amino-5-oxo-1-phenyl-3-pyrrolidineacetate

Product 1

HCID 67795074cis-4-[(1H-Indol-2-ylcarbonyl)amino]-5-oxo-1-phenyl-3-pyrrolidineacetic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of indole-2-carboxylic acid in DMF is added 1 equivalent of 1,1-carbonyldiimidazole. After stirring for 4 h at room temperature a solution of the aminopyrrolidinone of Example 68 in DMF is added. After stirring for 12 h at room temperature the reaction mixture is evaporated in vacuo to give a residue which is chromatographed on silica gel to give the desired amide. To a solution of the amide in 1:4 EtOH/THF is added a solution of lithium hydroxide (1.4 equiv) in H2O and the resulting solution is stirred for 2 h at room temperature. The reaction mixture is then acidified to pH=2 with 1N HCl. Removal of the solvent gives a residue which is chromatographed on silica gel to give the title carboxylic acid as a single enantiomer.

Workup

  1. additionis added
  2. customis evaporated in vacuo
  3. customto give a residue which
  4. customis chromatographed on silica gel

Sources & evidence

ORD record
ord-0fc7578a9ee24a789655f209a989651b
Source dataset
uspto-grants-1994_05
Patent number
US05314886

Reaction notes

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