Cesium fluoride → 1-{[2,4-bis(methyloxy)phenyl]methyl}-3-methyl-4-[4-(trifluoromethyl)phenyl]-1H-pyrrole-2,5-dione

HRID 1513336Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:4]=1[CH2:11][N:12]1[C:16](=[O:17])[C:15]([CH3:18])=[C:14](Br)[C:13]1=[O:20].[F:21][C:22]([F:33])([F:32])[C:23]1[CH:28]=[CH:27][C:26](B(O)O)=[CH:25][CH:24]=1.[F-].[Cs+]>[Cl-].C([N+](CC)(CC1C=CC=CC=1)CC)C.C1(C)C=CC=CC=1.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=[CH:5][C:4]=1[CH2:11][N:12]1[C:13](=[O:20])[C:14]([C:26]2[CH:27]=[CH:28][C:23]([C:22]([F:33])([F:32])[F:21])=[CH:24][CH:25]=2)=[C:15]([CH3:18])[C:16]1=[O:17]

Participants

Conditions

Temperature: 90 °C

Procedure

{[2,4-bis(methyloxy)phenyl]methyl}-3-bromo-4-methyl-1H-pyrrole-2,5-dione (P9, 3.3, 9.7 mmol), [4-(trifluoromethyl)phenyl]boronic acid (3.68 g, 19.40 mmol), bis(triphenylphosphine)palladium(ii) chloride (0.601 g, 0.91 mmol) and cesium fluoride (3.98 g, 26.2 mmol) and N,N-diethyl-N-(phenylmethyl)ethanaminium chloride (0.22 g, 0.970 mmol) were dissolved in Toluene (60 mL)/Water (60.0 mL) and the reaction mixture was stirred at 90° C. overnight. Toluene was evaporated under reduced pressure and a saturated solution of NH4Cl was added. The aqueous phase was extracted with DCM, solvent was eliminated under reduced pressure and crude product by flash chromatography (Biotage SiO2, eluent: Cy/AcOEt 98:2; fraction volume: 45 mL) affording 1-{[2,4-bis(methyloxy)phenyl]methyl}-3-methyl-4-[4-(trifluoromethyl)phenyl]-1H-pyrrole-2,5-dione (P10, 4.55 g, 11.22 mmol)

Workup

customToluene was evaporated under reduced pressure
additiona saturated solution of NH4Cl was added
extractionThe aqueous phase was extracted with DCM, solvent

Sources & evidence

ORD record: ord-ab6cb544f80e496a894af18528d2791b
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08217168B2

Reaction notes

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