2,3-Dichloro-5,6-dicyano-1,4-benzoquinone → 2-Chloro-4-(pyridin-2-yl)pyrimidine

Temperature

0 °C

To a solution of 2-chloropyrimidine (8.0 g, 50 mmol) in THF (100 mL) at −78° C., n-BuLi (24 mL, 60 mmol) was added dropwise under N2. After addition, the reaction solution was stirred for 30 min, a solution of 2-bromopyridine (5.75 g, 50 mmol) in THF (50 mL) was added in portions. The reaction mixture was stirred at −30° C. for 30 min and at 0° C. for 45 min., then quenched with AcOH (5 mL) and water (1 mL). A solution of DDQ (16.3 g, 80 mmol) in THF (50 mL) was added in portions and the mixture was stirred at room temperature for 45 min. TLC (petroleum:EtOAc=5:1) indicated the reaction was complete. The reaction mixture was cooled to 0° C. and 3N NaOH (142 mL) was added and stirred for 30 min. The aqueous layer was extracted with EtOAc (50 mL×3). The combined extract was dried over Na2SO4, concentrated and purified by chromatography, eluted with petroleum ether:EtOAc (10:1 to 5:1) to give title compound (4.8 g, 50%) as a light yellow solid.

1. additionAfter addition
2. stirringThe reaction mixture was stirred at −30° C. for 30 min and at 0° C. for 45 min.
3. customquenched with AcOH (5 mL) and water (1 mL)
4. stirringthe mixture was stirred at room temperature for 45 min
5. stirringstirred for 30 min
6. extractionThe aqueous layer was extracted with EtOAc (50 mL×3)
7. extractionThe combined extract
8. dry with materialwas dried over Na2SO4
9. concentrationconcentrated
10. custompurified by chromatography
11. washeluted with petroleum ether:EtOAc (10:1 to 5:1)

ORD record

ord-fd1fa3858c504664b65f17b445d32c08

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09056865B2