Sodium Carbonate → 5-(3,5-dichlorophenyl)-1H-indole-2-carboxylic acid ethyl ester

HRID 646168Notes

Reaction equation

HRID 646168 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([C:14]=1Cl)=[CH:12][C:11](Br)=[CH:10][CH:9]=2)=[O:5])[CH3:2].[Cl:17][C:18]1[CH:19]=[C:20](B(O)O)[CH:21]=[C:22]([Cl:24])[CH:23]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Na+].[Na+]>CC#N.CC(O)C.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([C:20]1[CH:19]=[C:18]([Cl:17])[CH:23]=[C:22]([Cl:24])[CH:21]=1)=[CH:10][CH:9]=2)=[O:5])[CH3:2]

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 27343313,5-Dichlorophenylboronic acidHCID 28330549ethyl 5-bromo-3-chloro-1H-indole-2-carboxylate

Product 1

HCID 686972085-(3,5-dichlorophenyl)-1H-indole-2-carboxylic acid ethyl esterYield 69.2%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 3776IsopropanolSolventHCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of 5-bromo-3-chloro-1H-indole-2-carboxylic acid ethyl ester (500 mg, 1.86 mmol) and 3,5-dichlorophenyl boronic acid (530 mg, 2.78 mmol) in a mixture of MeCN (26 mL) and i-PrOH (3.3 mL) at room temperature under argon, was added Pd(OAc)2 (12 mg, 0.05 mmol), Ph3P (40 mg, 0.15 mmol) and Na2CO3 (2M aq., 16 mL) and the resulting mixture was heated at reflux for 3 h. After cooling to room temperature the reaction was diluted with water (20 mL) and extracted with EtOAc (3×30 mL). The combined organic extracts were washed with water, brine and dried (MgSO4). Solvent removal and purification by chromatography afforded the sub-title compound (430 mg, 69%).

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureat reflux for 3 h
  3. extractionextracted with EtOAc (3×30 mL)
  4. washThe combined organic extracts were washed with water, brine
  5. dry with materialdried (MgSO4)
  6. customSolvent removal and purification by chromatography

Sources & evidence

ORD record
ord-355bf65a6dc247d8a6a2db493828223c
Source dataset
uspto-grants-2010_04
Patent number
US07705023B2

Reaction notes

Loading…