Dichloromethane → methyl 1-methyl-5-phenyl-1H-pyrrole-2-carboxylate

HRID 1359657Notes

Reaction equation

HRID 1359657 reaction equation
Br[C:2]1[N:6]([CH3:7])[C:5]([C:8]([O:10][CH3:11])=[O:9])=[CH:4][CH:3]=1.[C:12]1(B(O)O)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C([O-])([O-])=O.[Na+].[Na+].C(Cl)Cl>COCCOC.O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Pd]>[CH3:7][N:6]1[C:2]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:3][CH:4]=[C:5]1[C:8]([O:10][CH3:11])=[O:9]

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 22350505Methyl 5-bromo-1-methyl-1H-pyrrole-2-carboxylate

Product 1

HCID 22350789methyl 1-methyl-5-phenyl-1H-pyrrole-2-carboxylateYield 96%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

The product from step 152a is added to a solution of tetrakis(triphenylphosphine)palladium(O) (0.530 g, 0.459 mmol) in 90 mL of ethylene glycol dimethyl ether. The resulting solution is stirred under nitrogen for 5 min and then phenylboronic acid (1.34 g, 11.0 mmol) is added followed by a solution of Na2CO3 (19.5 g, 183 mmol) in 90 mL of H2O. The mixture is heated at reflux for 24 hours. The reaction mixture is allowed to cool to rt, 100 mL of CH2Cl2 is added, and the layers are separated. The aqueous layer is extracted with CH2Cl2 (3×50 mL) and combined organic layers are dried over MgSO4, filtered, and concentrated in vacuo. The crude product is purified by flash column chromatography (5% EtOAc in hexane) to give 1.89 g of methyl 1-methyl-5-phenyl-1H-pyrrole-2-carboxylate as a yellow oil (96% yield). MS for Cl3H13NO2 (ESI) (M+H)+ m/z 216.1.

Workup

  1. temperatureThe mixture is heated
  2. temperatureat reflux for 24 hours
  3. customthe layers are separated
  4. extractionThe aqueous layer is extracted with CH2Cl2 (3×50 mL)
  5. dry with materialare dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product is purified by flash column chromatography (5% EtOAc in hexane)

Sources & evidence

ORD record
ord-83daa990a5a14ee7b07e19bea6085370
Source dataset
uspto-grants-2003_07
Patent number
US06599916B2

Reaction notes

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