Ethyl vinyl ether → HCID 57067109, compound

10 g of methyl (4aS, 7S, 7aR)-1,4a,5,6,7,7a-hexahydro-1-hydroxy-7-methylcyclopenta[c]pyran-4-carboxylate obtained in Definite Example 4 was dissolved in 100 ml of dichloromethane, and after 50 ml of ethyl vinyl ether and then100 mg of pyridinium paratoluenesulfonate were added while the reaction mixture was being cooled by ice. Then, the reaction mixture was stirred at room temperature for 24 hours. The reaction mixture solution was extracted with dichloromethane. After 200 ml of dichloromethane was added to the reaction mixture solution, the organic layer was washed with 50 ml of saturated sodium hydrogen carbonate solution and 50 ml of saturated sodium chloride solution, and was then dried by magnesium sulfate. After filtration, the solvent was distilled off under a reduced pressure. 2.5 g of the resulting yellow oily substance, i.e., methyl (1S, 4aS, 7S, 7aR)-1-[1-(ethoxy)ethoxy]-1,4a,5,6,7,7a-hexahydro-7-methylcyclopenta[c]pyran-4-carboxylate was dissolved in 30 ml of anhydrous tetrahydrofuran without purification, and 26.5 ml of diisobutylaluminum hydride (1.0 mol THF solution) was added dropwise while the reaction mixture was being cooled by ice and being stirred (in an argon gas atmosphere). After the reaction mixture was stirred at the same temperature for 2 hours, 2 ml of acetone was added. Next, 3.4 ml of water, 3.4 ml of an aqueous sodium hydroxide and 10 ml of water were added in the order named, and the reaction mixture was stirred. When insoluble matters were precipitated, the precipitate was filtrated and the solvent was distilled off under a reduced pressure. 2.3 g of the resulting colorless oily substance, i.e., (1S, 4aS, 7S, 7aR)-1-[1-(ethoxy)ethoxy]-1,4a,5,6,7,7a-hexahydro-4-(hydroxymethyl)-7-methylcyclopenta[c]pyran was dissolved in 30 ml of anhydrous dichloro-methane without purification, and 4 ml of pyridine was added. Next, 4 ml of acetic anhydride was added dropwise, and after 50 mg of 4-dimethylaminopyridine was added, the reaction mixture was stirred at room temperature for 5 hours. The reaction mixture was extracted with 150 ml of ethyl acetate. The organic layer which was washed by 100 ml of water, 2N hydrochloric acid solution (100 ml×2), saturated sodium hydrogen carbonate solution (100 ml×2) and 100 ml of saturated sodium chloride solution was dried by anhydrous magnesium sulfate, and the solvent was distilled off under a reduced pressure. The resulting colorless oily substance was purified by column chromatography using 50 g of silica gel, and there was obtained 1.6 g of colorless oily substance (1S, 4aS, 7S, 7aR)-4-(acetoxymethyl)-1-[1-(ethoxy)ethoxy]-1,4a,5, 6,7,7a-hexahydro-7-methylcyclopenta[c]pyran (yield=60%) from the hexane:ether=7:3 eluent.

1. temperaturewas being cooled by ice
2. extractionThe reaction mixture solution was extracted with dichloromethane
3. additionAfter 200 ml of dichloromethane was added to the reaction mixture solution
4. washthe organic layer was washed with 50 ml of saturated sodium hydrogen carbonate solution and 50 ml of saturated sodium chloride solution
5. dry with materialwas then dried by magnesium sulfate
6. filtrationAfter filtration
7. distillationthe solvent was distilled off under a reduced pressure
8. additionwas added dropwise while the reaction mixture
9. temperaturewas being cooled by ice and being
10. stirringstirred (in an argon gas atmosphere)
11. stirringAfter the reaction mixture was stirred at the same temperature for 2 hours
12. stirringthe reaction mixture was stirred
13. customWhen insoluble matters were precipitated
14. filtrationthe precipitate was filtrated
15. distillationthe solvent was distilled off under a reduced pressure
16. dissolution2.3 g of the resulting colorless oily substance, i.e., (1S, 4aS, 7S, 7aR)-1-[1-(ethoxy)ethoxy]-1,4a,5,6,7,7a-hexahydro-4-(hydroxymethyl)-7-methylcyclopenta[c]pyran was dissolved in 30 ml of anhydrous dichloro-methane without purification, and 4 ml of pyridine
17. additionwas added
18. additionNext, 4 ml of acetic anhydride was added dropwise
19. additionafter 50 mg of 4-dimethylaminopyridine was added
20. stirringthe reaction mixture was stirred at room temperature for 5 hours
21. extractionThe reaction mixture was extracted with 150 ml of ethyl acetate
22. washThe organic layer which was washed by 100 ml of water, 2N hydrochloric acid solution (100 ml×2), saturated sodium hydrogen carbonate solution (100 ml×2) and 100 ml of saturated sodium chloride solution
23. dry with materialwas dried by anhydrous magnesium sulfate
24. distillationthe solvent was distilled off under a reduced pressure
25. customThe resulting colorless oily substance was purified by column chromatography

ORD record

ord-67f471bb96eb4a5781aca32b2010cd87

Source dataset

uspto-grants-1994_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05374653