Ethanol → 4-[4-(3,5-dichloro-phenyl)-4-trifluoromethyl-3,4-dihydro-2H-pyrrol-2-yl]-2-methyl-benzoic acid ethyl ester

HRID 1844634Notes

Reaction equation

HRID 1844634 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:12][C:11]([C:17]3[CH:22]=[C:21]([Cl:23])[CH:20]=[C:19]([Cl:24])[CH:18]=3)([C:13]([F:16])([F:15])[F:14])[CH:10]=[N:9]2)=[CH:4][C:3]=1[CH3:25].[C:26]([O-:29])(=[O:28])C.[Na+].[C]=O.[CH2:33](O)[CH3:34]>CN(C)C=O.ClCCl.[Pd+2].ClC1C=C[C-](P(C2C=CC=CC=2)C2C=CC=CC=2)C=1Cl.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH2:33]([O:29][C:26](=[O:28])[C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:12][C:11]([C:17]3[CH:22]=[C:21]([Cl:23])[CH:20]=[C:19]([Cl:24])[CH:18]=3)([C:13]([F:14])([F:16])[F:15])[CH:10]=[N:9]2)=[CH:4][C:3]=1[CH3:25])[CH3:34]

Participants

7

Reactant 4

HCID 702EthanolHCID 517045Sodium AcetateHCID 866589832-(4-bromo-3-methyl-phenyl)-4-(3,5-dichloro-phenyl)-4-trifluoromethyl-3,4-dihydro-2H-pyrroleHCID 178418416HCID 178418416, compound

Product 1

HCID 672174284-[4-(3,5-dichloro-phenyl)-4-trifluoromethyl-3,4-dihydro-2H-pyrrol-2-yl]-2-methyl-benzoic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 178478475HCID 178478475, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(4-bromo-3-methyl-phenyl)-4-(3,5-dichloro-phenyl)-4-trifluoromethyl-3,4-dihydro-2H-pyrrole (Example 14) (7.0 g) in a mixture of ethanol (60 ml) and dimethylformamide (20 ml), was added dichloro 1,1′-bis(diphenylphosphino)ferrocene palladium(II) dichloromethane adduct (“Pd(dppf)Cl2”) (0.8 g) and sodium acetate (1.4 g) at ambient temperature. The reaction mixture was stirred in a pressure reactor in an atmosphere of carbon monoxide (6 bar) at 85° C. for 16 hours. The reaction mixture was cooled to ambient temperature, the ethanol was evaporated and aqueous sodium hydrogen carbonate (saturated) (200 ml) and ethyl acetate (250 ml) were added. The phases were separated and the organic phase was dried over sodium sulfate and concentrated. The residue was purified by chromatography on silica gel (eluent: gradient of 0-4% v/v methanol in dichloromethane) to give 4-[4-(3,5-dichloro-phenyl)-4-trifluoromethyl-3,4-dihydro-2H-pyrrol-2-yl]-2-methyl-benzoic acid ethyl ester (2.8 g). 1H-NMR (CDCl3, 400 MHz): 8.04-7.06 (m, 7H), 5.46-5.06 (m, 1H), 4.35 (m, 2H), 3.27-3.79 (m, 1H), 2.59 (m, 3H), 2.38-2.10 (m, 1H), 1.39 (m, 3H) ppm.

Workup

  1. customthe ethanol was evaporated
  2. additionaqueous sodium hydrogen carbonate (saturated) (200 ml) and ethyl acetate (250 ml) were added
  3. customThe phases were separated
  4. dry with materialthe organic phase was dried over sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by chromatography on silica gel (eluent

Sources & evidence

ORD record
ord-f7aa16bd60d94146ab8fb9ec00b85fd4
Source dataset
uspto-grants-2015_02
Patent number
US08946447B2

Reaction notes

Loading…