反应详情

温度

-70 °C

n-Butyl lithium (0.045 mol) was added at −70° C. under N2 flow to a solution of 4-phenyl-thiazole (0.045 mol) in diethyl ether (50 ml). The mixture was stirred at −70° C. for 90 minutes. A solution of 2-[3-chloro-4-(4-chlorobenzoyl)phenyl]-1,2,4-triazine-3,5-(2H,4H)-dione (0.015 mol) in THF (10 ml) was added at −70° C. The mixture was stirred at −70° C. for 1 hour, then poured out into ice water, neutralized with HCl 3N and extracted with EtOAc. The organic layer was separated, dried, filtered and the solvent was evaporated. The residue was purified by column chromatography oversilica gel (eluent: CH2Cl2/CH3OH 98/2). The desired fraction was repurified by HPLC (eluent: CH3OH/(NH4OAc 1% in H2O) 80/20). The pure fractions were collected and the solvent was evaporated, yielding 0.83 g (11%) of (±)-2-[3-chloro-4-[(4-chlorophenyl)hydroxy(4-phenyl-2-thiazolyl)methyl]phenyl]-1,2,4-triazine-3,5(2H,4H)-dione (interm. 71).

1. stirringThe mixture was stirred at −70° C. for 1 hour
2. extractionextracted with EtOAc
3. customThe organic layer was separated
4. customdried
5. filtrationfiltered
6. customthe solvent was evaporated
7. customThe residue was purified by column chromatography oversilica gel (eluent: CH2Cl2/CH3OH 98/2)
8. customThe desired fraction was repurified by HPLC (eluent: CH3OH/(NH4OAc 1% in H2O) 80/20)
9. customThe pure fractions were collected
10. customthe solvent was evaporated