反应详情

温度

50 °C

The pyrazole 53-6 (300 mg, 0.803 mmol) was dissolved in acetonitrile (8 mL). K2CO3 (212 mg, 1.61 mmol) and 3,5-dichlorobenzyl bromide (231 mg, 0.964 mmol) were added, and the resulting mixture was warmed to 50° C. and stirred overnight. The reaction mixture was cooled to room temperature and diluted with ethyl acetate and water. The aqueous phase was extracted with ethyl acetate. Combined organic phases were washed with water and brine, dried over Na2SO4, filtered, and concentrated to give a yellow oil. Purification by column chromatography (ISCO chromatography system, SiO2, elution with 10 to 20% ethyl acetate in hexane) provided two sets of fractions. A pale yellow oil (152 mg, Rf=0.5, 40% ethyl acetate in hexane) provided a 1H NMR consistent with the previously isolated 53-7a. Another yellow oil (38 mg, mixture of spots by TLC) provided a 1H NMR consistent with a mixture of compounds. Further purification of this material by column chromatography (ISCO chromatography system, SiO2, elution with 10 to 20% ethyl acetate in hexane) provided a colorless oil (23 mg, Rf=0.58, 40% ethyl acetate in hexane) consistent with 2-{2-[2-(3,5 dichloro-benzyl)-2H-pyrazol-3-yl]-1-methoxycarbonyl-ethylamino}-4-methyl-pentanoic acid benzyl ester 53-7b. The proposed structure was supported by 2D NMR methods (NOESY, HMBC and HMQC).

1. temperatureThe reaction mixture was cooled to room temperature
2. extractionThe aqueous phase was extracted with ethyl acetate
3. washCombined organic phases were washed with water and brine
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated
7. customto give a yellow oil
8. customPurification
9. washby column chromatography (ISCO chromatography system, SiO2, elution with 10 to 20% ethyl acetate in hexane)
10. customprovided two sets of fractions
11. custompreviously isolated 53-7a
12. additionAnother yellow oil (38 mg, mixture of spots by TLC)
13. customprovided a 1H NMR
14. additionconsistent with a mixture of compounds
15. customFurther purification of this material
16. washby column chromatography (ISCO chromatography system, SiO2, elution with 10 to 20% ethyl acetate in hexane)