反应详情

The compound prepared in Example 230 (0.090 g) and lithium hydroxide hydrate (0.011 g) were combined in methanol (1 mL), tetrahydrofuran (1 mL) and water (0.1 mL) and allowed to stir for 48 hours. The reaction was concentrated, pumped to dryness and used without further purification. The crude acid was combined with the compound prepared in Example 9 (0.11 g, 0.31 mmol), 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide (0.069 g, 0.36 mmol), diisopropylethylamine (0.16 g, 1.2 mmol) and 1-hydroxybenzotriazole hydrate (0.049 g, 0.36 mmol) in dichloromethane (2.5 mL). The reaction was sonicated briefly to aid dissolution and then stirred for 24 hours. The crude reaction was concentrated and then dissolved in methanol and treated with 2N hydrochloric acid. After stirring for 15 minutes, this solution was concentrated and then partitioned between ethyl acetate and sodium hydrogen carbonate aqueous solution. The organic phase was dried over magnesium sulfate, filtered, concentrated and purified by column chromatography using an eluant of 4% methanol/dichloromethane to provide the title compound (0.023 g) with the following physical data.

1. concentrationThe reaction was concentrated
2. customused without further purification
3. customThe reaction was sonicated briefly
4. dissolutiondissolution
5. stirringstirred for 24 hours
6. customThe crude reaction
7. concentrationwas concentrated
8. dissolutiondissolved in methanol
9. additiontreated with 2N hydrochloric acid
10. stirringAfter stirring for 15 minutes
11. concentrationthis solution was concentrated
12. custompartitioned between ethyl acetate and sodium hydrogen carbonate aqueous solution
13. dry with materialThe organic phase was dried over magnesium sulfate
14. filtrationfiltered
15. concentrationconcentrated
16. custompurified by column chromatography