反应详情

温度

0 °C

Under an argon atmosphere 4-(tert-butoxycarbonylamino)-butyric acid (1.58 g, 8 mmol) is dissolved in 20 mL dry THF and cooled to 0° C. Diisopropyl ethylamine (1.18 g, 9 mmol) is added, the mixture cooled to −20° C., and chloroformic acid isobutylester (1.15 g, 8 mmol) added. The mixture is stirred at this temperature for 5 min, and nitroso-pyrimidine 38 (Example 21, 2.64 g, 7 mmol) dissolved in 20 mL dry THF is added via a syringe. The reaction mixture is allowed to warm to room temperature, heated to 55° C. and stirred at this temperature over night. After cooling to room temperature, the mixture is poured into 100 mL of 1 N HCl and the product extracted with ethyl acetate (300 mL). The combined organic phases are washed with water and brine, subsequently dried over MgSO4 and the solvent evaporated. The residue is adsorbed on SiO2 and purified by flash column chromatography (cyclohexane/ethyl acetate 1:2 to 1:10) to yield the title compound as a blue solid (1.96 g, 3.53 mmol, 50.4%). From the crude material, an analytical sample is recrystallized from ethyl acetate.

1. temperaturethe mixture cooled to −20° C.
2. additionis added via a syringe
3. temperatureto warm to room temperature
4. temperatureheated to 55° C.
5. stirringstirred at this temperature over night
6. temperatureAfter cooling to room temperature
7. extractionthe product extracted with ethyl acetate (300 mL)
8. washThe combined organic phases are washed with water and brine
9. dry with materialsubsequently dried over MgSO4
10. customthe solvent evaporated
11. custompurified by flash column chromatography (cyclohexane/ethyl acetate 1:2 to 1:10)