Potassium Phosphate, Tribasic → Tert-butyl 4-(4-phenylpyrimidin-2-yl)piperazine-1-carboxylate

Temperature

115 °C

tert-Butyl 4-(4-chloropyrimidin-2-yl)piperazine-1-carboxylate (300 mg, 1.0 mmol) and phenylboronic acid (183 mg, 1.5 mmol) were dissolved in toluene (10 mL) and the solution was purged with argon for 10 min. Potassium phosphate (426 mg, 2.0 mmol) was added to the reaction mixture, followed by a catalytic amount of Pd2(dba)3 (9 mg, 0.01 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (23 mg, 0.04 mmol). The reaction mixture was then heated to 115° C. for 10 h, cooled to room temperature, diluted with EtOAc, and filtered through Celite. The organic layer was washed with water and brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica 60-120 mesh, eluent 30% EtOAc in petroleum ether) to get tert-butyl 4-(4-phenylpyrimidin-2-yl)piperazine-1-carboxylate (250 mg, yield 73%). 1H NMR (300 MHz, MeOD) δ 8.28-8.23 (m, 3H), 7.46-7.43 (m, 3H), 7.34 (m, 1H), 3.80-3.77 (m, 4H), 3.56-3.53 (m, 4H), 1.48 (s, 9H). MS (ESI) m/z: Calculated for C19H24N4O2: 340.19. found: 341.2 (M+H)+

1. customthe solution was purged with argon for 10 min
2. temperaturecooled to room temperature
3. filtrationfiltered through Celite
4. washThe organic layer was washed with water and brine
5. dry with materialdried over anhydrous Na2SO4
6. concentrationconcentrated under reduced pressure
7. customThe crude product was purified by column chromatography (silica 60-120 mesh, eluent 30% EtOAc in petroleum ether)

ORD record

ord-0c2d35e705de48c09bf052df294fbd2a

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08981084B2