Water → 3-Benzyl-7-(4-tert-butoxycarbonyl-piperazin-1-yl)-indole-1,2-dicarboxylic acid 2-benzyl ester 1-tert-butyl ester

HRID 18177Notes

Reaction equation

HRID 18177 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][C:15]=2[N:17]2[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]2)[C:10]([CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)=[CH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Li]C(C)(C)C.Cl[C:43]([O:45][CH2:46][C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)=[O:44].O>C1COCC1.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][C:15]=2[N:17]2[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:28])([CH3:29])[CH3:27])=[O:24])[CH2:19][CH2:18]2)[C:10]([CH2:30][C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)=[C:9]1[C:43]([O:45][CH2:46][C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)=[O:44])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 962WaterHCID 10387Benzyl chloroformateHCID 685857503-Benzyl-7-(4-tert-butoxycarbonyl-piperazin-1-yl)-indole-1-carboxylic acid tert-butyl esterHCID 178418306HCID 178418306, compound

Product 1

HCID 685868203-Benzyl-7-(4-tert-butoxycarbonyl-piperazin-1-yl)-indole-1,2-dicarboxylic acid 2-benzyl ester 1-tert-butyl esterYield 39%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 3-benzyl-7-(4-tert-butoxycarbonyl-piperazin-1-yl)-indole-1-carboxylic acid tert-butyl ester (200 mg, 0.41 mmol) in THF (10 ml) was cooled to −78° C., and t-BuLi (1 ml, 1.7 M in pentane) was added. After stirring at −78° C. for 20 minutes, 0.15 ml of benzyl chloroformate was added and the reaction was allowed to warm up to room temperature for 30 minutes. Water was slowly added, followed by EtOAc. The organic layer was separated and washed with water and brine. After drying over MgSO4, the organic fraction was concentrated in vacuo and the resulting residue was purified by flash chromatography to give 3-benzyl-7-(4-tert-butoxycarbonyl-piperazin-1-yl)-indole-1,2-dicarboxylic acid 2-benzyl ester 1-tert-butyl ester as a yellow solid (100 mg, 39%). MS: (M+H)+ 626.4.

Workup

  1. temperatureto warm up to room temperature for 30 minutes
  2. customThe organic layer was separated
  3. washwashed with water and brine
  4. dry with materialAfter drying over MgSO4
  5. concentrationthe organic fraction was concentrated in vacuo
  6. customthe resulting residue was purified by flash chromatography

Sources & evidence

ORD record
ord-50639c0a2e814e65aa5afb4b46faac78
Source dataset
uspto-grants-2010_06
Patent number
US07741326B2

Reaction notes

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