Ethyl Acetate → ethyl 3-(4-chloro-2-fluorophenyl)-5-(trifluoromethyl)-1H-pyrrole-2-carboxylate

HRID 623743Notes

Reaction equation

HRID 623743 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:12]=[CH:11][NH:10][C:9]=2[C:13]([O:15][CH2:16][CH3:17])=[O:14])=[C:4]([F:18])[CH:3]=1.OP([O-])([O-])=O.[K+].[K+].[C:26](S(Cl)(=O)=O)([F:29])([F:28])[F:27].CCOC(C)=O>C1C=NC2C3N=CC=CC=3C=CC=2C=1.C1C=NC2C3N=CC=CC=3C=CC=2C=1.C1C=NC2C3N=CC=CC=3C=CC=2C=1.O.[Cl-].[Cl-].[Ru+2].O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:12]=[C:11]([C:26]([F:29])([F:28])[F:27])[NH:10][C:9]=2[C:13]([O:15][CH2:16][CH3:17])=[O:14])=[C:4]([F:18])[CH:3]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 24450Potassium Phosphate, DibasicHCID 79000Trifluoromethanesulfonyl chloride2×HCID 89987937ethyl 3-(4-chloro-2-fluorophenyl)-1H-pyrrole-2-carboxylate

Product 1

HCID 86711833ethyl 3-(4-chloro-2-fluorophenyl)-5-(trifluoromethyl)-1H-pyrrole-2-carboxylateYield 40.3%

Reagents, catalysts & solvents 2

HCID 16212249dichlorotris(1,10-phenanthroline)-ruthenium(II) hydrateCatalyst2×HCID 962WaterSolvent

Conditions

Temperature
27.5 °C

Procedure

To a mixture of ethyl 3-(4-chloro-2-fluorophenyl)-1H-pyrrole-2-carboxylate (2.00 g, 7.47 mmol), K2HPO4 (3.90 g, 22.4 mmol) and dichlortris(1,10-phenanthroline)-ruthenium(II) hydrate (106 mg, 0.149 mmol) in argon degassed dry MeCN (24 mL) was added CF3SO2Cl (1.59 mL, 14.9 mmol). The reaction mixture was stirred for 18 h at a temperature of 25-30° C. adjacent to a fluorescent light bulb (E27-32W, 4000K, 65 mA). The reaction mixture was diluted with argon degassed dry MeCN (24 mL). Extra reagents were added: CF3SO2Cl (398 μL, 3.73 mmol) and dichlortris(1,10-phenanthroline)-ruthenium(II) hydrate (106 mg, 0.149 mmol). The reaction mixture was stirred for 3 d at a temperature of 25-30° C. adjacent to a fluorescent light bulb. Subsequently, EtOAc (100 mL) and H2O (100 mL) were added. The aqueous layer was extracted with EtOAc (50 mL). The combination of organic layers was washed with saturated aqueous NaHCO3 and with brine, dried (Na2SO4) and the solvent was evaporated. The crude product was purified by flash chromatography (silica, gradient heptane/EtOAc, 1:0→4:1) to give a yellow solid, which was crystallised from hot heptane to provide 1.01 g (40%) of the desired product as colourless crystals.

Workup

  1. customdegassed dry MeCN (24 mL)
  2. additionThe reaction mixture was diluted with argon
  3. customdegassed dry MeCN (24 mL)
  4. additionExtra reagents were added
  5. extractionThe aqueous layer was extracted with EtOAc (50 mL)
  6. washThe combination of organic layers was washed with saturated aqueous NaHCO3 and with brine
  7. dry with materialdried (Na2SO4)
  8. customthe solvent was evaporated
  9. customThe crude product was purified by flash chromatography (silica, gradient heptane/EtOAc, 1:0→4:1)
  10. customto give a yellow solid, which
  11. customwas crystallised from hot heptane

Sources & evidence

ORD record
ord-7526cec6d9794942958c38fff64c192f
Source dataset
uspto-grants-2016_04
Patent number
US09302988B2

Reaction notes

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