Water → 1-(tert-Butyloxycarbonyl-methyl)-1H-indole-2-carboxylic acid ethyl ester

HRID 526307Notes

Reaction equation

HRID 526307 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]([O:12][CH2:13][CH3:14])=[O:11].Br[CH2:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18].C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C>[C:20]([O:19][C:17](=[O:18])[CH2:16][N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[C:2]1[C:10]([O:12][CH2:13][CH3:14])=[O:11])([CH3:23])([CH3:22])[CH3:21]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 73125Ethyl indole-2-carboxylateHCID 79177tert-Butyl bromoacetate

Product 1

HCID 543470691-(tert-Butyloxycarbonyl-methyl)-1H-indole-2-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of ethyl 1H-indole-2-carboxylate (5.68 g, 30 mmol), tert-butyl 2-bromoacetate (6.44 g, 33 mmol), and potassium carbonate in 60 mL of DMF was heated to 80° C. for 2 days. The TLC showed that the reaction stopped at around 50% completion. The reaction was worked up by the addition of water and the aqueous phase was extracted with EtOAc (2×30 mL). The combined organic phase was washed with brine, dried over Na2SO4, filtered and evaporated. The residue was purified by Combiflash (40 g silica gel cartridge, 0-30% EtOAc in hexane) to afford the desired product.

Workup

  1. extractionthe aqueous phase was extracted with EtOAc (2×30 mL)
  2. washThe combined organic phase was washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified by Combiflash (40 g silica gel cartridge, 0-30% EtOAc in hexane)

Sources & evidence

ORD record
ord-56d32c3a30314fe79858f9a356bb728b
Source dataset
uspto-grants-2016_05
Patent number
US09345905B2

Reaction notes

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