反应详情

4-(9-Acetylthiononyl)-7-methoxymethoxy-3-(4-methoxymethoxyphenyl)-3-methylchroman (40.0 mg, 0.0735 mmol) was dissolved in methanol (1 ml) under nitrogen, 2N—NaOH (0.5 ml) was added dropwise thereto, and the mixture was stirred at room temperature for 30 minutes. After the reaction was completed, the reaction mixture was cooled, and 2N-HCl aqueous solution was poured thereinto. This solution was extracted with chloroform and washed with saturated saline solution. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The residue thus obtained was added to a solvent mixture of methylene chloride (1 ml) and water (0.5 ml), N-chlorosuccinimide (39.3 mg, 0.294 mmol) was added, and the resulting mixture was stirred for 15 minutes. After the reaction was completed, saturated aqueous NAHCO3 solution was added thereto. The mixture was extracted with methylene chloride and washed with saturated saline solution. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure to give a mixture containing 4-(9-chlorosulfonylnonyl)-7-methoxymethoxy-3-(4-methoxymethoxyphenyl)-3-methylchroman. 4,4,5,5,5-Pentafluoropentylcarbamic acid t-butylester (61.8 mg, 0.221 mmol) was dissolved in methylene chloride (1 ml), TFA (1 ml) was added dropwise thereto, and the mixture was stirred at room temperature for 15 minutes. After the reaction was completed, the solvent was removed under reduced pressure. The residue thus obtained was dissolved in methylene chloride (1 ml) and cooled. To this solution was added a mixture containing triethylamine (0.051 ml, 0.37 mmol) and 4-(9-chlorosulfonylnonyl)-7-methoxymethoxy-3-(4-methoxymethoxyphenyl)-3-methylchroman dissolved in methylene chloride (1 ml), which was then stirred for 1 hour. After the reaction was completed, the organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The residue thus obtained was subjected to silica gel column chromatography (n-hexane:ethyl acetate=1:1) to give 7-methoxymethoxy-3-(4-methoxymethoxyphenyl)-3-methyl-4-[9-(4,4,5,5,5-pentafluoropentylaminosulfonyl)nonyl]chroman (8.0 mg, yield 16%).

1. temperaturethe reaction mixture was cooled
2. extractionThis solution was extracted with chloroform
3. washwashed with saturated saline solution
4. dry with materialThe organic layer was dried over magnesium sulfate
5. concentrationconcentrated under reduced pressure
6. customThe residue thus obtained
7. additionwas added
8. stirringthe resulting mixture was stirred for 15 minutes
9. additionsaturated aqueous NAHCO3 solution was added
10. extractionThe mixture was extracted with methylene chloride
11. washwashed with saturated saline solution
12. dry with materialThe organic layer was dried over magnesium sulfate
13. concentrationconcentrated under reduced pressure
14. customto give a mixture
15. stirringthe mixture was stirred at room temperature for 15 minutes
16. customthe solvent was removed under reduced pressure
17. customThe residue thus obtained
18. temperaturecooled
19. additionTo this solution was added a mixture
20. stirringwhich was then stirred for 1 hour
21. dry with materialthe organic layer was dried over magnesium sulfate
22. concentrationconcentrated under reduced pressure
23. customThe residue thus obtained