反应详情

A solution of potassium hydroxide (3.4 g) in water (20 ml) was added to a solution of ethyl 2-cyano-2-(1-benzyl-4-(3,5-dimethylphenyl)piperidin-4-yl)ethanoate (4.7 g) (see Preparation 8) in ethanol (24 ml) and the mixture microwaved at 345 kPa (100 psi)/100% power for 2.5 hours. The solvent was removed under reduced pressure and the residue azeotroped with toluene to remove any residual water. The residue was dissolved in ethanol (100 ml), cooled in an ice-bath and the solution saturated with hydrogen chloride gas. The mixture was left to stand at room temperature overnight before re-saturating the solution with hydrogen chloride gas and leaving to stand for a further 24 hours. The solution was filtered and the solvent removed from the filtrate under reduced pressure to give a residue which was dissolved in saturated aqueous sodium carbonate solution and extracted twice with dichloromethane. The organic phases were combined, dried over anhydrous sodium sulphate and the solvent removed under reduced pressure to give a residue which was chromatographed on silica gel eluting with a solvent gradient of 97:3 changing to 90:10, by volume, dichloromethane:methanol to give the title compound (2.0 g) as an oil.

1. customthe mixture microwaved at 345 kPa (100 psi)/100% power for 2.5 hours
2. customThe solvent was removed under reduced pressure
3. customthe residue azeotroped with toluene
4. customto remove any residual water
5. dissolutionThe residue was dissolved in ethanol (100 ml)
6. temperaturecooled in an ice-bath
7. waitThe mixture was left
8. concentrationbefore re-saturating the solution with hydrogen chloride gas
9. customleaving
10. waitto stand for a further 24 hours
11. filtrationThe solution was filtered
12. customthe solvent removed from the filtrate under reduced pressure
13. customto give a residue which
14. extractionextracted twice with dichloromethane
15. dry with materialdried over anhydrous sodium sulphate
16. customthe solvent removed under reduced pressure
17. customto give a residue which
18. customwas chromatographed on silica gel eluting with a solvent gradient of 97:3 changing to 90:10, by volume, dichloromethane