反应详情

Sodium hydride in mineral oil (60%, 65 mg, 1.63 mmol) was suspended in 3 mL of tetrahydrofuran. To this suspension was added 3 mL of a solution of 6-phenylpiperidin-2-one (235 mg, 1.34 mmol) and the mixture was stirred at ambient temperature for 30 minutes. The resulting solution was transferred via syringe to solution of 4-nitrophenylchloroformate (269 mg, 1.33 mmol) in tetrahydrofuran (4 mL) which had already been chilled to −78° C. The reaction mixture was stirred at −78° C. for 2 hours and then at ambient temperature for 30 minutes. The reaction mixture was then evaporated to dryness. One third of the resulting residue (150 mg, 0.441 mmol) was dissolved in 5 mL of dichloromethane. 4-cyano-4-phenylpiperidine propylamine (113 mg, 0.464 mmol) and triethylamine (139 mL, 0.997 mmol) were added to this solution, and the resulting yellow mixture was stirred at ambient temperature for 18 hours, and then evaporated to dryness. The resulting residue was purified by “flash” chromatography (97:3:0.3 dichloromethane:methanol:ammonium hydroxide). The product fractions were evaporated to give a yellow oil. The residue was purified by “flash” chromatography (1:1 ethyl acetate:hexanes). The product fractions were evaporated to dryness. The residue was then treated with HCl-saturated ethyl acetate, evaporated to dryness, and reconcentrated from diethyl ether twice to give the title compound as a solid.

1. temperaturehad already been chilled to −78° C
2. stirringThe reaction mixture was stirred at −78° C. for 2 hours
3. waitat ambient temperature for 30 minutes
4. customThe reaction mixture was then evaporated to dryness
5. stirringthe resulting yellow mixture was stirred at ambient temperature for 18 hours
6. customevaporated to dryness
7. customThe resulting residue was purified by “flash” chromatography (97:3:0.3 dichloromethane:methanol:ammonium hydroxide)
8. customThe product fractions were evaporated
9. customto give a yellow oil
10. customThe residue was purified by “flash” chromatography (1:1 ethyl acetate:hexanes)
11. customThe product fractions were evaporated to dryness
12. additionThe residue was then treated with HCl-saturated ethyl acetate
13. customevaporated to dryness