Triphenylphosphine → 2-Fluoro-6-methylbenzonitrile

Temperature

80 °C

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.

1. customA 10 L round bottom flask equipped with adapter
2. customdegassed under vacuum
3. custompurged with N2 three times
4. customthe mixture was degassed under vacuum
5. custompurged with N2 three times
6. customthe mixture was degassed under vacuum
7. custompurged with N2 three times
8. temperatureThe reaction mixture was heated to 80° C. for 16 h
9. temperatureto cool to RT
10. additionThe solution was added to a 2.0 L aqueous solution of 1N NH4OH, which
11. extractionwas extracted three times with 1.5 L EtOAc
12. washwashed with 2 L brine
13. dry with materialdried over Na2SO4
14. filtrationfiltered
15. concentrationconcentrated
16. custompurification
17. customwas then purified by chromatography (PE/EA=10:1)

ORD record

ord-fc3b503618f84dcbb6d2618e9799c8de

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09062070B2