反应详情

温度

10 °C

1-Benzyl-4-ethoxycarbonylpyridinium bromide (580 g, 1.80 mol) is suspended in a mixture of ethanol (900 ml) and water (900 ml), and thereto is added sodium borohydride (74.9 g, 1.98 mol) in portions while the temperature of the reaction mixture is kept at a temperature below 10° C. The reaction mixture is stirred at 10° C. for three hours. The reaction mixture is concentrated under reduced pressure, and the residue is dissolved in chloroform. The mixture is washed with water, dried over sodium sulfate, and concentrated under reduced pressure to remove the solvent. The residue is dissolved in chloroform (500 ml), and thereto is added dropwise ethyl chloroformate (215 g, 1.98 mol) under reflux over a period of one hour. The mixture is further refluxed for 30 minutes, and concentrated under reduced pressure. To the residue are added conc. hydrochloric acid (504 g) and water (150 g), and the mixture is refluxed for 10 hours. The reaction mixture is cooled to room temperature, and concentrated under reduced pressure. To the residue is added isopropyl alcohol (500 ml), and the mixture is stirred. The precipitated crystals are collected by filtration with suction, and washed with a small amount of ether, and dried with air to give 1,2,5,6-tetrahydroisonicotinic acid hydrochloride (151.7 g, 52%), as white crystals.

1. customis kept at a temperature below 10° C
2. concentrationThe reaction mixture is concentrated under reduced pressure
3. dissolutionthe residue is dissolved in chloroform
4. washThe mixture is washed with water
5. dry with materialdried over sodium sulfate
6. concentrationconcentrated under reduced pressure
7. customto remove the solvent
8. dissolutionThe residue is dissolved in chloroform (500 ml)
9. temperatureunder reflux over a period of one hour
10. temperatureThe mixture is further refluxed for 30 minutes
11. concentrationconcentrated under reduced pressure
12. additionTo the residue are added conc. hydrochloric acid (504 g) and water (150 g)
13. temperaturethe mixture is refluxed for 10 hours
14. temperatureThe reaction mixture is cooled to room temperature
15. concentrationconcentrated under reduced pressure
16. additionTo the residue is added isopropyl alcohol (500 ml)
17. stirringthe mixture is stirred
18. filtrationThe precipitated crystals are collected by filtration with suction
19. washwashed with a small amount of ether
20. customdried with air