反应详情

To a solution of 0.160 g (1.000 mmol) of 4,5,6,7-tetrahydrofuro[2,3-c]pyridine hydrochloride, 0.246 g (1.1 mmol) of 9-fluorenone-2-carboxylic acid and 0.55 ml (4.0 mmol) of triethylamine in 30 ml of dichloromethane, 0.24 g (1.5 mmol) of diethyl cyanophosphonate was added dropwise under ice-cooling, followed by overnight stirring at room temperature. This mixture was poured into water, followed by 2 extractions with dichloromethane. The combined organic layer was washed with water and dried over anhydrous sodium sulfate; the solvent was distilled off under reduced pressure. The resulting crude product was dissolved in 10 ml of acetic acid; 0.135 ml (1.50 mmol) of 50% aqueous dimethylamine and 0.122 ml (1.50 mmol) of 37% aqueous formaldehyde were added, followed by stirring at 100° C. for 60 minutes. After the solvent was distilled off under reduced pressure, the residual solution was alkalified with 5% aqueous sodium hydrogen carbonate and extracted with dichloromethane 2 times. The combined organic layer was washed with water and dried over anhydrous sodium sulfate; the solvent was distilled off under reduced pressure. The resulting crude product was purified by silica gel column chromatography (ethyl acetate/methanol=5/1) to yield the desired product.

1. temperaturecooling
2. extractionfollowed by 2 extractions with dichloromethane
3. washThe combined organic layer was washed with water
4. dry with materialdried over anhydrous sodium sulfate
5. distillationthe solvent was distilled off under reduced pressure
6. dissolutionThe resulting crude product was dissolved in 10 ml of acetic acid
7. stirringby stirring at 100° C. for 60 minutes
8. distillationAfter the solvent was distilled off under reduced pressure
9. extractionextracted with dichloromethane 2 times
10. washThe combined organic layer was washed with water
11. dry with materialdried over anhydrous sodium sulfate
12. distillationthe solvent was distilled off under reduced pressure
13. customThe resulting crude product was purified by silica gel column chromatography (ethyl acetate/methanol=5/1)