Potassium Phosphate, Tribasic → 2-chloro-4-cyclopropyl-5-fluoroPyrimidine

Temperature

67 °C

5-Fluoro-2,4-dichloropyrimidine (5 g, 29.9 mmol), cyclopropyl boronic acid (2.57 g, 29.9 mmol), potassium phosphate tribasic (15.89 g, 74.9 mmol) and PdCl2(dppf)-dichloromethane adduct (1.22 g, 1.50 mmol) were added to a dry flask. The flask was degassed with argon and then tetrahydrofuran (150 ml) was added. The reaction mixture was degassed with argon for five minutes, and then heated to 67° C. After 12 hours, the reaction mixture was cooled to room temperature, diluted with ethyl acetate (1000 mL), washed with brine, dried over magnesium sulfate, filtered and concentrated. The residue was purified by flash chromatography on silica gel (EtOAc/hexane gradient) to afford 2-chloro-4-cyclopropyl-5-fluoropyrimidine (4.1 g, 23.8 mmol, 79% yield). MS ESI: [M+H]+ m/z 172.9. 1H NMR (500 MHz, DMSO-d6) δ 8.66 (d, J=2.0 Hz, 1H); 2.34-2.26 (m, 1H); 1.26-1.20 (m, 2H); 1.12-1.08 (m, 2H).

1. customThe flask was degassed with argon
2. additiontetrahydrofuran (150 ml) was added
3. customThe reaction mixture was degassed with argon for five minutes
4. temperaturethe reaction mixture was cooled to room temperature
5. additiondiluted with ethyl acetate (1000 mL)
6. washwashed with brine
7. dry with materialdried over magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated
10. customThe residue was purified by flash chromatography on silica gel (EtOAc/hexane gradient)

ORD record

ord-ace8fa046a1f4307b68498ccac2a2f2e

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08551984B2