Sodium Hydroxide → HCID 23149883, compound

Temperature

-78 °C

Phenyllithium (0.94 M, 27 ml) was dissolved in diethyl ether (50 ml), and the mixture was cooled to −78° C. 1-Benzyl-3-methyl-4-piperidone (KANTO CHEMICAL CO. INC., 5 g) was added, and the mixture was stirred for 2 hr. After completion of the reaction, water was added, and the mixture was extracted three times with ethyl acetate. The organic layer was dried and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (elution solvent: hexane-ethyl acetate (4:1-0:1)). Phosphoric acid (40 g) and diphosphorus pentoxide (45 g) were added to the obtained oil, and the mixture was stirred with heating at 100° C. for 5 hr. After completion of the reaction, the reaction mixture was poured into water, basified with 1N sodium hydroxide and extracted four times with hexane. The organic layer was washed with water, and dried. The solvent was evaporated under reduced pressure to give a brown oil. The oil was dissolved in 1,2-dichloroethane. The mixture was cooled to 0° C. and 1-chloroethyl chloroformate (857 mg) was added. After heating under reflux for 5 hr, the reaction solution was concentrated. Methanol (10 ml) was added and the mixture was heated under reflux for 2 hr. After completion of the reaction, the reaction mixture was basic (pH=9) with a 1N aqueous sodium hydroxide solution, and extracted three times with chloroform. The organic layer was dried and the solvent was evaporated under reduced pressure to give 5-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (1.00 g, yield 90%).

1. additionwas added
2. extractionthe mixture was extracted three times with ethyl acetate
3. customThe organic layer was dried
4. customthe solvent was evaporated under reduced pressure
5. customThe obtained residue was purified by silica gel column chromatography (elution solvent: hexane-ethyl acetate (4:1-0:1))
6. additionPhosphoric acid (40 g) and diphosphorus pentoxide (45 g) were added to the obtained oil
7. stirringthe mixture was stirred
8. temperaturewith heating at 100° C. for 5 hr
9. customAfter completion of the reaction
10. extractionextracted four times with hexane
11. washThe organic layer was washed with water
12. customdried
13. customThe solvent was evaporated under reduced pressure
14. customto give a brown oil
15. temperatureThe mixture was cooled to 0° C.
16. temperatureAfter heating
17. temperatureunder reflux for 5 hr
18. concentrationthe reaction solution was concentrated
19. additionMethanol (10 ml) was added
20. temperaturethe mixture was heated
21. temperatureunder reflux for 2 hr
22. customAfter completion of the reaction
23. extractionextracted three times with chloroform
24. customThe organic layer was dried
25. customthe solvent was evaporated under reduced pressure

ORD record

ord-f6b56a7365b141adb0743876815f99d2

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07994196B2