反应详情

In a 500-mL four-necked round-bottom flask equipped with a stirrer, dropping funnel, reflux condenser with gas lead-off, a thermometer and a gas inlet are placed 100 mL benzyl alcohol and 0.937 g (0.0312 mole) sodium hydride (80% in oil) is introduced while flushing with a protective gas. The resulting suspension is then subsequently stirred for 30 minutes. Thereafter, a solution of 52.55 g (0.124 mole) (±)-1,4-dihydro-5-isopropoxy-2-methyl-4-(2-trifluoromethylphenyl)-1,6-naphthyridine-3-carboxylic acid ethyl ester in 200 mL benzyl alcohol is allowed to run in, followed by stirring for 15 hours at 120° C. After cooling to ambient temperature, the reaction mixture is stirred with 1 L of water and 400 mL dichloromethane. After separating the phases, the aqueous phase is again stirred with 300 mL dichloromethane. The dichloromethane phases are combined and washed twice with 300 mL amounts of water. The dichloromethane phase is dried over anhydrous sodium sulfate. After filtering, the dichloromethane is distilled off on a rotary evaporator and subsequently the benzyl alcohol is distilled off under oil pump vacuum (54°-65° C./3-5 mm Hg). The distillation residue is dissolved in 600 mL hot cyclohexane and the solution is cooled to 0° C. while stirring. The precipitate obtained is filtered off with suction and subsequently washed with 100 mL n-hexane. The filter cake is then dried at 80° C. Yield: 43.9 g (72.8% of theory); mp 131° C. with a purity of 99.4 relative %.

1. customIn a 500-mL four-necked round-bottom flask equipped with a stirrer
2. temperaturereflux condenser with gas lead-off, a thermometer and a gas inlet
3. additionis introduced
4. customwhile flushing with a protective gas
5. stirringby stirring for 15 hours at 120° C
6. customAfter separating the phases
7. stirringthe aqueous phase is again stirred with 300 mL dichloromethane
8. washwashed twice with 300 mL amounts of water
9. dry with materialThe dichloromethane phase is dried over anhydrous sodium sulfate
10. filtrationAfter filtering
11. distillationthe dichloromethane is distilled off on a rotary evaporator
12. distillationsubsequently the benzyl alcohol is distilled off under oil pump vacuum (54°-65° C./3-5 mm Hg)
13. dissolutionThe distillation residue is dissolved in 600 mL hot cyclohexane
14. temperaturethe solution is cooled to 0° C.
15. stirringwhile stirring
16. customThe precipitate obtained
17. filtrationis filtered off with suction
18. washsubsequently washed with 100 mL n-hexane
19. customThe filter cake is then dried at 80° C