Water → 5-(2-tert-butoxycarbonyl-vinyl)-1H-indole-2-carboxylic acid ethyl ester

HRID 49055Notes

Reaction equation

HRID 49055 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11](Br)=[CH:10][CH:9]=2)=[O:5])[CH3:2].[C:16]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])(=[O:19])[CH:17]=[CH2:18].C(N(CC)CC)C.O>C(O)(=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.ClCCl>[CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([CH:18]=[CH:17][C:16]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[CH:10][CH:9]=2)=[O:5])[CH3:2]

Participants

8

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 15458tert-Butyl acrylateHCID 259091Ethyl 5-Bromoindole-2-carboxylate

Product 1

HCID 695871265-(2-tert-butoxycarbonyl-vinyl)-1H-indole-2-carboxylic acid ethyl esterYield 28.5%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 5-bromoindole-2-carboxylic acid ethyl ester (2.68 g, 10 mmol), tert-butyl acrylate (4.4 mL, 30 mmol) and dichlorobis(triphenylphosphine)palladium(II) (0.7 g, 1 mmol) and triethylamine (17 mL) in acetic acid (17 mL) was heated at 120° C. in a closed vessel for 6 hrs. The cooled reaction mixture was poured into water and dichloromethane. The biphasic mixture was filtered through a pad of celite and the aqueous layer was extracted with dichloromethane (2×). The combined organic layers were washed with saturated sodium bicarbonate solution, brine, dried and concentrated. The residue was purified by column chromatography (10% of ethyl acetate in hexanes) to give 900 mg (28%) of 5-(2-tert-butoxycarbonyl-vinyl)-1H-indole-2-carboxylic acid ethyl ester.

Workup

  1. customThe cooled reaction mixture
  2. filtrationThe biphasic mixture was filtered through a pad of celite
  3. extractionthe aqueous layer was extracted with dichloromethane (2×)
  4. washThe combined organic layers were washed with saturated sodium bicarbonate solution, brine
  5. customdried
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography (10% of ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-9653ef1145b4482bb4edf3f452aeadc5
Source dataset
uspto-grants-2004_03
Patent number
US06706709B2

Reaction notes

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