反应详情

温度

0 °C

In a 250 ml three-necked flask, triethylamine (3.49 ml, 2.50.10−2 mol, 1.15 eq.) is added dropwise to a solution, cooled to 0° C., of the acid obtained in Step D (4.62 g, 2.18. 10−2 mol) in a mixture of acetone (95 ml) and water (5.4 ml). Ethyl chloroformate (2.71 ml, 2.83.10−2 mol, 1.30 eq.) is then slowly added at 0° C.; evolution of gas is visible. The mixture is stirred at 0° C. for 30 minutes; after it has been established, on TLC (CH2Cl2), that the starting material has disappeared, a solution of sodium azide (1.89 g, 2.83.10−2 mol, 1.30 eq.) in water (9.2 ml) is added at 0° C. The mixture is maintained at that temperature for one hour. The mixture is poured into an ice/water mixture and is then extracted with ether. The ethereal phases are washed with water, then dried over Na2SO4 and evaporated in vacuo without heating. The acyl azide is taken up in 50 ml of anhydrous toluene and then heated at 80° C. until nitrogen is no longer evolved. After evaporating off the toluene, the oil corresponding to the isocyanate is heated at 100° C. together with a 20% hydrochloric acid solution (52 ml) for 3 hours; the mixture is stirred for one night at ambient temperature. The reaction mixture is diluted with water, filtered through filter paper and extracted with ether. The aqueous phase of pH=1 is rendered basic using solid sodium carbonate and is then extracted three times with dichloromethane. The combined organic phases are washed with water and dried over K2CO3. After evaporating off the solvent under reduced pressure, the amine is obtained in the form of an oil (820 mg). The solid, having been filtered and taken up in dichloromethane, is treated in the same manner as the filtrate. The amine so obtained is converted into the hydrochloride after being solubilised in ether and treated with a 4N ethereal hydrogen chloride solution. After drying, the title product is obtained in the form of a white solid.

1. temperatureThe mixture is maintained at that temperature for one hour
2. extractionis then extracted with ether
3. washThe ethereal phases are washed with water
4. dry with materialdried over Na2SO4
5. customevaporated in vacuo
6. temperaturewithout heating
7. temperatureheated at 80° C. until nitrogen
8. customAfter evaporating off the toluene
9. temperaturethe oil corresponding to the isocyanate is heated at 100° C. together with a 20% hydrochloric acid solution (52 ml) for 3 hours
10. stirringthe mixture is stirred for one night at ambient temperature
11. additionThe reaction mixture is diluted with water
12. filtrationfiltered
13. filtrationthrough filter paper
14. extractionextracted with ether
15. extractionis then extracted three times with dichloromethane
16. washThe combined organic phases are washed with water
17. dry with materialdried over K2CO3
18. customAfter evaporating off the solvent under reduced pressure