反应详情

温度

0 °C

Lithium diisopropylamide (2.0 molar solution in tetrahydrofuran/ethylbenzene/heptane, 1.46 ml, 0.0029 mole) was added dropwise to a chilled solution of 5-amino-4-chloro-3-methylisothiazole (0.44 g, 0.0029 mole) [preparation as in Example 1, Step 1] in tetrahydrofuran (20 ml) and the solution was stirred at 0° C. for 1 hour. A solution of methyl 2-[2-(2,2-dimethylpropyl)benzoxazol-5-yl]propionate (0.80 g, 0.0029 mole) [from previous step] in tetrahydrofuran (5 ml) was added dropwise and once the addition was complete the mixture was stirred at 0° C. for 30 minutes and then at room temperature overnight. The mixture was quenched with water, acidified with aqueous ammonium chloride solution and extracted with ethyl acetate. The organic extract was dried over anhydrous magnesium sulfate, filtered and the filtrate evaporated in vacuo. Further purification by flash column chromatography, eluting with ethyl acetate:hexane at 1:4 by volume gave N-(4-chloro-3-methylisothiazol-5-yl)-2-[2-(2,2-dimethylpropyl)benzoxazol-5-yl]propionamide as a colourless solid.

1. additiononce the addition
2. stirringwas stirred at 0° C. for 30 minutes
3. customat room temperature
4. customovernight
5. customThe mixture was quenched with water
6. extractionextracted with ethyl acetate
7. extractionThe organic extract
8. dry with materialwas dried over anhydrous magnesium sulfate
9. filtrationfiltered
10. customthe filtrate evaporated in vacuo
11. customFurther purification by flash column chromatography
12. washeluting with ethyl acetate