反应详情

To a solution of trans-methyl 4-(chloro(hydroxyimino)methyl)cyclohexanecarboxylate (0.900 g, 4.10 mmol) and 4-cyclopentenylmorpholine (1.23 ml, 8.19 mmol) in dichloromethane (21 ml) was added triethylamine (0.714 ml, 5.12 mmol) at 0-5° C. The reaction mixture was allowed to warm to room temperature and stirred for 20 h. The solvent was evaporated. The residue was redissolved in 6 M aqueous hydrogen chloride solution (20.5 ml) and stirred at reflux for 4 h. After cooling to room temperature the reaction mixture was poured on ice, basified with 2 M aqueous sodium hydroxide solution (80 ml) and washed with two 50-ml portions of ethyl acetate. The combined organic layers were extracted with two 50-ml portions of 1 M aqueous sodium hydroxide solution. The combined aqueous layers were acidified to pH 2-3 by addition of concentrated hydrochloric acid and extracted with three 100-ml portions of ethyl acetate. The combined organic extracts were dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was triturated in tert-butyl methyl ether (50 ml). The precipitate was removed by filtration. The filtrate was concentrated in vacuo. The residue was purified by flash chromatography with n-heptane/ethyl acetate as eluent to give the title compound (0.060 g, 6%) as off-white solid. MS m/e: 234 ([M−H]−)

1. customThe solvent was evaporated
2. dissolutionThe residue was redissolved in 6 M aqueous hydrogen chloride solution (20.5 ml)
3. stirringstirred
4. temperatureat reflux for 4 h
5. temperatureAfter cooling to room temperature the reaction mixture
6. additionwas poured on ice
7. washwashed with two 50-ml portions of ethyl acetate
8. extractionThe combined organic layers were extracted with two 50-ml portions of 1 M aqueous sodium hydroxide solution
9. additionThe combined aqueous layers were acidified to pH 2-3 by addition of concentrated hydrochloric acid
10. extractionextracted with three 100-ml portions of ethyl acetate
11. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
12. concentrationconcentrated in vacuo
13. customThe residue was triturated in tert-butyl methyl ether (50 ml)
14. customThe precipitate was removed by filtration
15. concentrationThe filtrate was concentrated in vacuo
16. customThe residue was purified by flash chromatography with n-heptane/ethyl acetate as eluent