反应详情

To a stirred solution of 4-(4-Cyano phenoxy)piperidine-1-carboxylic acid tert-butyl ester (21.25 g, 0.0704 moles) in dichloromethane (300 mL) was added trifluoroacetic acid (81.4 g, 0.714 moles) and stirred the reaction mass overnight at room temperature. After completion of reaction, solvent was evaporated under vacuum and the residue, thus obtained, was basified with 10% caustic lye solution. The reaction mass was extracted with ethyl acetate twice, the combined organic layer was dried over sodium sulphate and evaporated under reduced pressure. The crude product, thus obtained, was treated with cyclobutanone (5.18 g, 0.074 moles), acetic acid (4.89 g, 0.0815 moles) in ethylene dichloride (100 mL), and stirred for 4 hours at room temperature. Sodium triacetoxyborohydride (35.06 g, 0.165 moles) was added to the reaction mass in a single lot and the mixture was stirred at room temperature for 2 hours. The reaction mixture was quenched in water and basified with lye solution. The layers were separated and the aqueous layer was extracted with dichloromethane twice. The combined organic layers were dried over sodium sulfate, concentrated under vacuum and the residual mass was further purified by flash chromatography (dichloromethane: triethylamine, 9.5:0.5) to obtain the title compound 10.92 g (Yield: 60.5%).

1. customAfter completion of reaction, solvent
2. customwas evaporated under vacuum
3. customthe residue, thus obtained
4. extractionThe reaction mass was extracted with ethyl acetate twice
5. dry with materialthe combined organic layer was dried over sodium sulphate
6. customevaporated under reduced pressure
7. customThe crude product, thus obtained
8. stirringstirred for 4 hours at room temperature
9. stirringthe mixture was stirred at room temperature for 2 hours
10. customThe reaction mixture was quenched in water
11. customThe layers were separated
12. extractionthe aqueous layer was extracted with dichloromethane twice
13. dry with materialThe combined organic layers were dried over sodium sulfate
14. concentrationconcentrated under vacuum
15. customthe residual mass was further purified by flash chromatography (dichloromethane: triethylamine, 9.5:0.5)