Triphenylphosphine → 2-Fluoro-6-methylbenzonitrile

Participants

Reaction Conditions

Reaction Steps

A 10 L round bottom flask equipped with adapter, thermocouple and stir bar was charged with DMA (6 L) and degassed under vacuum and purged with N2 three times. To the mixture was added palladium tetrakis triphenylphosphine (87.5 g, 72.0 mmol) and the mixture was degassed under vacuum and purged with N2 three times. The reaction was heated to 80° C. for 30 min. 3-Fluoro-2-iodotoluene (575 g, 2.4 mol) and zinc cyanide (171.7 g, 1.46 mol) were added and the mixture was degassed under vacuum and purged with N2 three times. The reaction mixture was heated to 80° C. for 16 h and then allowed to cool to RT. The solution was added to a 2.0 L aqueous solution of 1N NH4OH, which was extracted three times with 1.5 L EtOAc, washed with 2 L brine, dried over Na2SO4, filtered and concentrated. The crude product was treated with mCPBA (˜0.2 equivalents) in cooled DCM to oxidize triphenylphosphine and facilitate purification, and was then purified by chromatography (PE/EA=10:1) to get the title compound.

Provenance & Evidence