反应详情

温度

80 °C

78.7 g (260 mmole) 1-(2-Chloro-phenyl)-3-(1-adamantyl)-propan-1-one, 77.5 g (2.1 eq.) urotropine and 72.6 g (2.7 eq.) of acetic anhydride were placed in a 500 ml roundbottom flask and the mixture was stirred at 80° C. for 4 h. Then 100 ml water and 100 ml 2M NaOH were added and the mixture was extracted two times with 200 ml dichloromethane each. The organic layer was washed two times with 100 ml saturated aqueous ammonium chloride and dried over magnesium sulphate. The solvent amount was reduced in vacuo to a total of 150 ml volume and the solution was added dropwise over a period of 2.5 h to 660 g of hot (70-75° C.) concentrated sulphuric acid. After stirring for an additional 30 min at 75° C. the mixture was allowed to stand overnight at room temperature. The mixture was given to approx. 500 g of ice and extracted three times with 150 ml dichloromethane each. The organic layer was washed twice with 150 ml of a saturated sodium bicarbonate solution and once with 100 ml of a saturated sodium chloride solution. After drying over magnesium sulphate the solvent was removed in vacuo. The product was purified by column chromatography on silica (heptane/dichloromethane 5:1) to yield 58 g (71%) of the desired product as a slightly off-white glassy solid. 1H-NMR (400 MHz, CDCl3): δ=7.39 (t, 1H, aromatic), 7.27 (d, 1H, aromatic), 7.21 (d, 1H, aromatic), 3.37 (dd, 1H, COCH), 2.70 (m, 2H, benzylic), 1.36-1.18 (m, 17H, aliphatic) ppm.

1. extractionthe mixture was extracted two times with 200 ml dichloromethane each
2. washThe organic layer was washed two times with 100 ml saturated aqueous ammonium chloride
3. dry with materialdried over magnesium sulphate
4. additionthe solution was added dropwise over a period of 2.5 h to 660 g of hot (70-75° C.) concentrated sulphuric acid
5. stirringAfter stirring for an additional 30 min at 75° C. the mixture
6. waitto stand overnight at room temperature
7. extractionextracted three times with 150 ml dichloromethane each
8. washThe organic layer was washed twice with 150 ml of a saturated sodium bicarbonate solution and once with 100 ml of a saturated sodium chloride solution
9. dry with materialAfter drying over magnesium sulphate the solvent
10. customwas removed in vacuo
11. customThe product was purified by column chromatography on silica (heptane/dichloromethane 5:1)