1-fluoro-2-iodo-3-methylbenzene

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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. A 10 L round bottom flask equipped with adapter degassed under vacuum purged with N2 three times the mixture was degassed under vacuum purged with N2 three times the mixture was degassed under vacuum purged with N2 three times The reaction mixture was heated to 80° C. for 16 h 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 concentrated purification was then purified by chromatography (PE/EA=10:1)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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 and extracted three times with 1.5 L EtOAc. The extracts were washed with 2 L brine, dried over Na2SO4, filtered and concentrated. The crude product was treated with mCPBA in cooled DCM and then purified by chromatography (PE/EA=10:1) to get the title compound. A 10 L round bottom flask equipped with adapter degassed under vacuum purged with N2 three times the mixture was degassed under vacuum purged with N2 three times the mixture was degassed under vacuum purged with N2 three times The reaction mixture was heated to 80° C. for 16 h to cool to RT The solution was added to a 2.0 L aqueous solution of 1N NH4OH extracted three times with 1.5 L EtOAc The extracts were washed with 2 L brine dried over Na2SO4 filtered concentrated The crude product was treated with mCPBA in cooled DCM purified by chromatography (PE/EA=10:1)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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 in cooled DCM and then purified by chromatography (PE/EA=10:1) to get the title compound. A 10 L round bottom flask equipped with adapter degassed under vacuum purged with N2 three times the mixture was degassed under vacuum purged with N2 three times the mixture was degassed under vacuum purged with N2 three times The reaction mixture was heated to 80° C. for 16 h 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 concentrated The crude product was treated with mCPBA in cooled DCM purified by chromatography (PE/EA=10:1)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 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 and extracted three times with 1.5 L EtOAc. The extracts were washed with 2 L brine, dried over Na2SO4, filtered and concentrated. The crude product was treated with mCPBA in cooled DCM and then purified by chromatography (PE/EA=10:1) to get the title compound. A 10 L round bottom flask equipped with adapter degassed under vacuum purged with N2 three times the mixture was degassed under vacuum purged with N2 three times the mixture was degassed under vacuum purged with N2 three times The reaction mixture was heated to 80° C. for 16 h to cool to RT The solution was added to a 2.0 L aqueous solution of 1N NH4OH extracted three times with 1.5 L EtOAc The extracts were washed with 2 L brine dried over Na2SO4 filtered concentrated The crude product was treated with mCPBA in cooled DCM purified by chromatography (PE/EA=10:1)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 5 L round bottom flask equipped with adapter, thermocouple and stir bar was charged with DMA (2.4 L) and degassed under vacuum and purged with N2 three times. Tetrakis was added to the mixture (35 g, 30.3 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 (230 g, 974 mmol) and zinc cyanide (68.7 g, 585 mmol) were added and the mixture was degassed under vacuum and purged with N2 three times. The mixture was heated to 80° C. for 16 hrs and allowed to cool to RT. The solution was added to 2.0 L aqueous solution of 1N NH4OH, which was then extracted three times with 1.5 L EtOAc, washed with 2 L brine, dried over Na2SO4, filtered, concentrated and purified by silica chromatography (PE/EA=10:1) to give the title compound. A 5 L round bottom flask equipped with adapter degassed under vacuum purged with N2 three times the mixture was degassed under vacuum purged with N2 three times the mixture was degassed under vacuum purged with N2 three times The mixture was heated to 80° C. for 16 hrs to cool to RT The solution was added to 2.0 L aqueous solution of 1N NH4OH, which was then extracted three times with 1.5 L EtOAc washed with 2 L brine dried over Na2SO4 filtered concentrated purified by silica chromatography (PE/EA=10:1)