反应详情

温度

50 °C

To a stirred solution of crude (R)-diethyl 1-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)azetidine-3,3-dicarboxylate (93 mg, 0.17 mmol) in MeOH (2 mL) was added 6 N NaOH (5 drops). The resulting solution was heated to 50° C. in a closed vial. After 24 h the solution was concentrated, dissolved in water, neutralized with 1N HCl, and heated at 100° C. After 15 h, additional 1N HCl was added, and the mixture was stirred at 105° C. for 24 h. The mixture was diluted with water and extracted with DCM and EA. The organic layers were combined, dried over Na2SO4, and purified by preparative HPLC to provide 25 mg (33%) of (R)-1-(4-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-inden-1-yl)azetidine-3-carboxylic acid 202. LCMS-ESI (m/z) calculated for C25H24N4O4: 444.5. found 445.2 [M+H]+, tR=2.55 min. Compound 203 was made in an analogous fashion.

1. concentrationAfter 24 h the solution was concentrated
2. dissolutiondissolved in water
3. temperatureheated at 100° C
4. additionadditional 1N HCl was added
5. additionThe mixture was diluted with water
6. extractionextracted with DCM and EA
7. dry with materialdried over Na2SO4
8. custompurified by preparative HPLC