反应详情

温度

55 °C

In a 1 liter round bottom flask, a solution of ethyl-N-benzyl-3-pyrrolidine carboxylate (21.8 g, 11.7 mmol) in 140 ml of 6N HCl was heated at reflux for 2.5 hours. The solution was cooled and the solvent was removed to dryness with a vacuum pump. The residue was then treated with thionyl chloride (100 ml) for 16 hours at room temperature. After the reaction, the excess thionyl chloride was vacuum stripped to dryness (60° C., 4 hours). To the residue in the flask was added 1,3-difluorobenzene (30 g, 26 mmol) followed by aluminum chloride (25 g, 18.7 mmol) in portions at room temperature. When the mixture turned homogeneous (in about 10 minutes) it was then heated at 55° C. for 1 hour. After the reaction was complete, excess 1,3-difluorobenzene was removed under reduced pressure. The residue was partitioned between ice/water and dichloromethane (700 ml) and basified with 50% NaOH solution to pH 10. The dichloromethane solution was washed with water and brine, then dried over anhydrous MgSO4. The solvent was stripped and the crude oil (31 g) was purified by flash chromatography over a silica gel column. The pure product thus obtained weighed 26 g (74%) as a yellow oil. An analytical sample was prepared by dissolving 4.2 g of the oil in ethanol and treating with an ethanol solution of oxalic acid (1.33 g, 14.8 mmol). To the mixture was added ether dropwise to cause crystallization. Recrystallization from ethanol and ether gave 2.63 g of (2,4-difluorophenyl)[1-(phenylmethyl)-3-pyrrolidinyl]methanone oxalate as white crystals, m.p.=114°-116° C.

1. temperatureat reflux for 2.5 hours
2. temperatureThe solution was cooled
3. customthe solvent was removed to dryness with a vacuum pump
4. additionThe residue was then treated with thionyl chloride (100 ml) for 16 hours at room temperature
5. customAfter the reaction
6. customstripped to dryness (60° C., 4 hours)
7. custom(in about 10 minutes) it
8. customexcess 1,3-difluorobenzene was removed under reduced pressure
9. customThe residue was partitioned between ice/water and dichloromethane (700 ml)
10. washThe dichloromethane solution was washed with water and brine
11. dry with materialdried over anhydrous MgSO4
12. customthe crude oil (31 g) was purified by flash chromatography over a silica gel column
13. customThe pure product thus obtained
14. customAn analytical sample was prepared
15. customcrystallization
16. customRecrystallization from ethanol and ether