Triethylamine → Methyl 3-chloro-4-((1-ethyl-3-indolylcarbonyl)amino)phenylacetate

HRID 1372689Notes

Reaction equation

HRID 1372689 reaction equation
[CH2:1]([N:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12]([OH:14])=O)=[CH:4]1)[CH3:2].C(Cl)(=O)C(Cl)=O.[Cl:21][C:22]1[CH:23]=[C:24]([CH2:29][C:30]([O:32][CH3:33])=[O:31])[CH:25]=[CH:26][C:27]=1[NH2:28].C(N(CC)CC)C>C(Cl)Cl>[Cl:21][C:22]1[CH:23]=[C:24]([CH2:29][C:30]([O:32][CH3:33])=[O:31])[CH:25]=[CH:26][C:27]=1[NH:28][C:12]([C:5]1[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[N:3]([CH2:1][CH3:2])[CH:4]=1)=[O:14]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 36971601-ethyl-1H-indole-3-carboxylic acidHCID 13616273Methyl 2-(4-amino-3-chlorophenyl)acetate

Product 1

HCID 17858879Methyl 3-chloro-4-((1-ethyl-3-indolylcarbonyl)amino)phenylacetateYield 88.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
15 °C

Procedure

To 1-ethylindole-3-carboxylic acid (160.2 mg, 0.847 mmol) were added methylene chloride (3.5 ml) and oxalyl chloride (108.9 μl, 1.270 mmol) under stirring at 15° C. The reaction mixture was stirred for 2.5 hours at room temperature. The solvent was then distilled off under reduced pressure. To the residue was added methylene chloride (3.5 ml). Under stirring at room temperature, a solution of methyl 3-chloro-4-aminophenylacetate (177.5 mg, 0.889 mmol) in methylene chloride (3.5 ml) and triethylamine (0.37 ml, 2.667 mmol) were added and the mixture was heated under reflux for 18 hours. After the reaction mixture was cooled to room temperature, the solvent was distilled off under reduced pressure. The residue was dissolved in chloroform. The resulting solution was washed with 1N HCl ad saturated saline, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to give methyl 3-chloro-4-((1-ethyl-3-indolylcarbonyl)amino)phenylacetate (277.7 mg, 88%) as a brown amorphous substance. The resulting compound was provided for the subsequent reaction without further purification.

Workup

  1. stirringThe reaction mixture was stirred for 2.5 hours at room temperature
  2. distillationThe solvent was then distilled off under reduced pressure
  3. additionTo the residue was added methylene chloride (3.5 ml)
  4. stirringUnder stirring at room temperature
  5. temperaturethe mixture was heated
  6. temperatureunder reflux for 18 hours
  7. temperatureAfter the reaction mixture was cooled to room temperature
  8. distillationthe solvent was distilled off under reduced pressure
  9. dissolutionThe residue was dissolved in chloroform
  10. washThe resulting solution was washed with 1N HCl ad saturated saline
  11. dry with materialdried over anhydrous sodium sulfate
  12. distillationThe solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-c872d94476db4c6cbd0217771009689e
Source dataset
uspto-grants-2007_01
Patent number
US07157487B2

Reaction notes

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