反应详情

n-Butyllithium (4.0 ml of a 2.5M solution in hexane) was added to a stirred solution of diisopropylamine (1.01 g) in dry tetrahydrofuran (30 ml) at -70° under an atmosphere of dry nitrogen. The solution was stirred at -70° for 0.17 hour, followed by 0.17 hour at 0° and then re-cooled to -70° . 4-Ethylpyrimidine (1.08 g) was added and the solution was stirred at -70° for 0.75 hour. A solution of 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazol-1-yl)ethanone (2.23 g) in dry tetrahydrofuran (30 ml) was added over 0.17 hour. The solution was stirred at -70° for 1 hour and then acetic acid (1 ml) was added. The solution was allowed to reach room temperature and was then diluted with water. The mixture was extracted three times with ethyl acetate and the combined extracts were washed with water then dried (Na2SO4 ). The solvent was evaporated and the residue was chromatographed on silica gel. Initial elution with ethyl acetate/hexane (3:2) gave recovered ketone starting material. Further elution with ethyl acetate gave, after combination and evaporation of appropriate fractions, the title compound, diastereoisomeric pair A, (0.305 g), m.p. 114°-115.5° (from ether/hexane).

1. waitfollowed by 0.17 hour at 0°
2. temperaturere-cooled to -70°
3. stirringthe solution was stirred at -70° for 0.75 hour
4. stirringThe solution was stirred at -70° for 1 hour
5. customto reach room temperature
6. extractionThe mixture was extracted three times with ethyl acetate
7. washthe combined extracts were washed with water
8. dry with materialthen dried (Na2SO4 )
9. customThe solvent was evaporated
10. customthe residue was chromatographed on silica gel
11. washInitial elution with ethyl acetate/hexane (3:2)
12. customgave
13. customrecovered ketone starting material
14. washFurther elution with ethyl acetate
15. customgave
16. customafter combination and evaporation of appropriate fractions