Tributylamine → tert-butyl 4-(2,5-difluorophenyl)-2-(3-fluorophenyl)-2,5-dihydro-1H-pyrrole-1-carboxylate

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Reaction Steps

To a flame dried flask equipped with stir bar was added tert-butyl 3-(2,5-difluorophenyl)-2,3-dihydro-1H-pyrrole-1-carboxylate (2-2, 0.088 g, 0.31 mmol), 3-fluoro-1-iodobenzene (0.070 g, 0.31 mmol), triphenylarsine (0.038 g, 0.13 mmol), tributylamine (0.15 mL, 0.62 mmol) and anhydrous DMF (2.0 mL). The resulting solution was purged, and filled with a nitrogen atmosphere. Palladium acetate (0.014 g, 0.06 mmol) was added in one portion, and the reaction was carefully returned to a nitrogen atmosphere. The reaction stirred under nitrogen for 24 h at 65° C. The reaction was then diluted with EtOAc (10 mL) and poured into 5% aq. NaHCO3 in a separatory funnel. The organic layer was washed with brine, separated and dried over magnesium sulfate. The organic layer was then filtered and concentrated to provide crude product. Purification by flash column chromatography (SiO2, 0-20% EtOAc/hexanes gradient) provided tert-butyl 4-(2,5-difluorophenyl)-2-(3-fluorophenyl)-2,5-dihydro-1H-pyrrole-1-carboxylate (4-1). LRMS m/z (M+H) 361.0 found, 361.1 required (M−15). Further transformations followed those described in Scheme 1.

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