反应详情

1-Methylcyclohexylcarbonyl chloride (1.6 g) was added dropwise to a mixture of L-aspartic acid β-benzyl ester (2.23 g), dichloromethane (30 ml) and triethylamine (30 ml) with ice-cooling and stirring. The resulting mixture was stirred with ice-cooling for an hour, washed with 1N hydrochloric acid and water and dried over anhydrous magnesium sulfate. The solvent was then distilled off and the oily residue (3.2 g) was dissolved in dimethoxyethane (30 ml). Acetic anhydride (4 ml), pyridine (4.8 ml) and 4-dimethylaminopyridine (0.12 g) were added and the mixture was refluxed for 1.5 hours. Acetic acid (2 ml) was added and the whole mixture was refluxed for 2.5 hours. The solvent was distilled off and water was added. The mixture was extracted with ethyl acetate and the ethyl acetate layer was washed with diluted hydrochloric acid, water, aqueous sodium hydrogen carbonate and water in that order, and dried over anhydrous magnesium sulfate. The residue (2.0 g) was purified by chromatography on silica gel (40 g) [eluent: hexane-acetone (9:1)] to give benzyl 3-(1-methylcyclohexylcarbonylamino)-4-oxovalerate as an oil; yield 1.2 g (34.8%).

1. temperaturecooling
2. stirringThe resulting mixture was stirred with ice-
3. temperaturecooling for an hour
4. washwashed with 1N hydrochloric acid and water
5. dry with materialdried over anhydrous magnesium sulfate
6. distillationThe solvent was then distilled off
7. dissolutionthe oily residue (3.2 g) was dissolved in dimethoxyethane (30 ml)
8. additionAcetic anhydride (4 ml), pyridine (4.8 ml) and 4-dimethylaminopyridine (0.12 g) were added
9. temperaturethe mixture was refluxed for 1.5 hours
10. additionAcetic acid (2 ml) was added
11. temperaturethe whole mixture was refluxed for 2.5 hours
12. distillationThe solvent was distilled off
13. additionwater was added
14. extractionThe mixture was extracted with ethyl acetate
15. washthe ethyl acetate layer was washed with diluted hydrochloric acid, water, aqueous sodium hydrogen carbonate and water in that order
16. dry with materialdried over anhydrous magnesium sulfate
17. customThe residue (2.0 g) was purified by chromatography on silica gel (40 g) [eluent: hexane-acetone (9:1)]