反应详情

温度

23 °C

A 2-L 3-necked round bottom flask fitted with a reflux condenser, a mechanical stirrer, and a glass stopper was charged with t-butyl alcohol (300 mL) and potassium 1-butoxide (68.7 g, 612 mmol, 1.04 equiv). The glass stopper was removed and, with efficient mechanical stirring, (1R,3R,4S)-p-menth-3-yl acetoacetate (1, 150 g, 624 mmol, 1.06 equiv) was added rapidly to the yellow slurry. The open neck of the reaction flask was fitted with a 100-mL addition funnel containing (E)-ethyl crotonate (73.2 mL, 588 mmol, 1 equiv). The largely solid reaction mixture was heated to reflux with a heating mantle. At this point, (E)-ethyl crotonate was added to the refluxing, dark yellow slurry over 15 min via the addition funnel. The addition funnel was replaced with a glass stopper and heating at reflux was continued. Solids were observed to dissolve within 1 h after addition of (E)-ethyl crotonate; the product began to crystallize from solution after about 1.5 h. After a total reflux period of 2.5 h (from addition of (E)-ethyl crotonate), heating was discontinued and the reaction mixture was allowed to cool to 23° C. The cooled reaction mixture was partitioned between aqueous sulfuric acid solution (5% v/v, 500 mL) and dichloromethane (600 mL). The aqueous layer was separated and extracted further with two 600-mL portions of dichloromethane. The combined organic layers were dried over sodium sulfate and then were concentrated. The solid residue was dissolved in boiling benzene (ca. 600 mL) and the resulting solution was allowed to cool slowly to 23° C. whereupon (1R,3R,4S)-p-menth-3-yl(1R,2S)-2-methyl-4,6-dioxocyclo-hexanecarboxylate (2) crystallized as a white powder (mp 180°-181° C., 64.5 g, 36%). To isolate the diastereomeric diketone product, (1R,3R,4S)-p-menth-3-yl(1S,2R)-2-methyl-4,6-dioxocyclohexanecarboxylate (3), the mother liquors were concentrated and the solid residue was dissolved in boiling ethyl acetate (ca. 200 mL). Hexanes (50 mL) were added to the hot solution and the mixture was allowed to cool to 23° C. Further cooling to -20° C. induced crystallization of diketone diastereomer 3 over a period of 12 h (mp 140°-141° C., 45 g, 25%). ##STR15##

1. customA 2-L 3-necked round bottom flask fitted with a reflux condenser, a mechanical stirrer
2. additionwas added rapidly to the yellow slurry
3. customThe open neck of the reaction flask was fitted with a 100-mL addition funnel
4. customThe largely solid reaction mixture
5. temperaturewas heated
6. temperatureto reflux with a heating mantle
7. temperatureheating
8. temperatureat reflux
9. dissolutionto dissolve within 1 h
10. customto crystallize from solution after about 1.5 h
11. temperatureAfter a total reflux period of 2.5 h
12. addition(from addition of (E)-ethyl crotonate)
13. temperatureheating
14. customThe cooled reaction mixture
15. customwas partitioned between aqueous sulfuric acid solution (5% v/v, 500 mL) and dichloromethane (600 mL)
16. customThe aqueous layer was separated
17. extractionextracted further with two 600-mL portions of dichloromethane
18. dry with materialThe combined organic layers were dried over sodium sulfate
19. concentrationwere concentrated
20. dissolutionThe solid residue was dissolved
21. temperatureto cool slowly to 23° C. whereupon (1R,3R,4S)-p-menth-3-yl(1R,2S)-2-methyl-4,6-dioxocyclo-hexanecarboxylate (2)
22. customcrystallized as a white powder (mp 180°-181° C., 64.5 g, 36%)