Cesium fluoride → 4-Chloro-6-phenylpyrimidine

Temperature

80 °C

Phenylboronic acid (3.05 g, 25 mmol) was added to a solution of 4,6-dichloropyrimidine (7.45 g, 50 mmol) in 50 mL of dimethoxyethane at 70° C. followed by cesium fluoride (7.60 g, 50.0 mmol). The resulting mixture was stirred for 5 minutes at 80° C. and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (II) (2.04 g, 2.5 mmol) was then added. The reaction mixture was stirred at 80° C. for one hour then evaporated. The residue was extract with ether (3×50 mL) and EtOAc (1×50 mL). The combined organic layers were washed with 100 mL saturated sodium carbonate solution (100 mL), dried over magnesium sulfate, filtered, and concentrated. The residue was purified by chromatography (Biotage 40 L eluting with 250 mL each of 0, 10, 20, 30, 40, 50, 60, 70, 80, and 100% dichloromethane/petroleum ether) to afford 2.20 g, (46.2%) of the product. MS 191.0 (AP+, 100).

1. stirringThe reaction mixture was stirred at 80° C. for one hour
2. customthen evaporated
3. extractionThe residue was extract with ether (3×50 mL) and EtOAc (1×50 mL)
4. washThe combined organic layers were washed with 100 mL saturated sodium carbonate solution (100 mL)
5. dry with materialdried over magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. customThe residue was purified by chromatography (Biotage 40 L eluting with 250 mL each of 0, 10, 20, 30, 40, 50, 60, 70, 80, and 100% dichloromethane/petroleum ether)

ORD record

ord-e1bbc2e3463f40cb973d7f1e1a8ab1f7

Source dataset

uspto-grants-2009_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07485641B2