反应详情

Chloroform (100 ml), was mixed with 10.1 g (56.6 mmol), of p-tert-butylbenzoic acid and 20.2 g of thionyl chloride, and the mixture was refluxed for 5 hours. The solvent and excess thionyl chloride were distilled off under reduced pressure and the residue was dissolved in a small amount of methanol. The solution was dropped to 17 ml of a 40% methylamine-methanol solution cooled on an ice bath. After dropping, the solution was taken out of the ice bath and stirred at room temperature for 48 hours. Then, 100 ml of 2N hydrochloric acid was added to the reaction mixture, which was extracted with dichloromethane, and after washing with water and saturated saline, respectively, the organic layer was dried with magnesium sulfate. After distilling off the solvent under reduced pressure, the resulting white crystals were dissolved in dichloromethane and the solution was washed with 1 liter of a saturated aqueous sodium hydrogen carbonate solution to remove p-tert-butylbenzoic acid, raw material. After the organic extract was dried with magnesium sulfate, the solvent was distilled off under reduced pressure to obtain 8.15 g (yield: 74.9%), of N-methyl-4-tert-butylbenzamide as white crystals. This was mixed with 110 ml of diethyl ether, 8.15 g (42.6 mmol), of N-methyl-4-tert-butylbenzamide and 2.88 g (85.2 mmol), of lithium aluminum hydride, and refluxed in nitrogen atmosphere for 6 hours. After the reflux, the reaction mixture was ice cooled and water was added thereto to decompose excess lithium aluminum hydride. Aluminum hydroxide deposited was filtered off and the filtrate was extracted with diethyl ether. After washing with water and saturated saline, respectively, the organic extract was dried with magnesium sulfate. The solvent was distilled off under reduced pressure and the resulting yellow oily substance was distilled under reduced pressure (115 to 118°C./10 mmHg), to obtain 3.69 g (yield: 48.9%), of the target compound as yellow oily substance.

1. temperaturethe mixture was refluxed for 5 hours
2. distillationThe solvent and excess thionyl chloride were distilled off under reduced pressure
3. dissolutionthe residue was dissolved in a small amount of methanol
4. additionThe solution was dropped to 17 ml of a 40% methylamine-methanol solution
5. temperaturecooled on an ice bath
6. additionThen, 100 ml of 2N hydrochloric acid was added to the reaction mixture, which
7. extractionwas extracted with dichloromethane
8. washafter washing with water and saturated saline
9. dry with materialrespectively, the organic layer was dried with magnesium sulfate
10. distillationAfter distilling off the solvent under reduced pressure
11. dissolutionthe resulting white crystals were dissolved in dichloromethane
12. washthe solution was washed with 1 liter of a saturated aqueous sodium hydrogen carbonate solution
13. customto remove p-tert-butylbenzoic acid, raw material
14. extractionAfter the organic extract
15. dry with materialwas dried with magnesium sulfate
16. distillationthe solvent was distilled off under reduced pressure
17. customto obtain 8.15 g (yield: 74.9%)
18. temperaturerefluxed in nitrogen atmosphere for 6 hours
19. temperaturecooled
20. filtrationAluminum hydroxide deposited was filtered off
21. extractionthe filtrate was extracted with diethyl ether
22. washAfter washing with water and saturated saline
23. extractionrespectively, the organic extract
24. dry with materialwas dried with magnesium sulfate
25. distillationThe solvent was distilled off under reduced pressure
26. distillationthe resulting yellow oily substance was distilled under reduced pressure (115 to 118°C./10 mmHg)
27. customto obtain 3.69 g (yield: 48.9%)