反应详情

To a solution of 4-(1-phenyl-methylene)-piperidine-1-carboxylic acid tert-butyl ester (30.0 g, 0.11 mol) in CHCl3 (300 mL) containing K2CO3 (22.5 g, 0.16 mol) was added a solution of Br2 (5.9 mL, 0.16 mol) in CHCl3 (50 mL) at 0° C. over 1 h. The mixture was allowed to stir for 1 h at room temperature and then it was diluted with water, the layers were separated and the aqueous phase extracted with CH2Cl2. The combined organic layers were washed (H2O, brine), dried (Na2SO4) and evaporated. The residue was dissolved in MeOH (300 mL) and a solution of NaOH (75 g, 1.88 mol) in H2O (250 mL) was slowly added, followed by another 100 mL of MeOH to maintain homogeneity. The mixture was heated at 40° C. for 4 hours and then most of the MeOH was removed in vacuo and the mixture was extracted with EtOAc (×3). The combined organic layers were washed, (H2O, brine), dried (Na2SO4) and evaporated. The residue was purified by flash chromatography (SiO2/hexane-EtOAc, 4:1) to afford the product (36.2 g, 94%) as a yellow-orange solid:

1. customthe layers were separated
2. extractionthe aqueous phase extracted with CH2Cl2
3. washThe combined organic layers were washed (H2O, brine)
4. dry with materialdried (Na2SO4)
5. customevaporated
6. dissolutionThe residue was dissolved in MeOH (300 mL)
7. temperatureto maintain homogeneity
8. temperatureThe mixture was heated at 40° C. for 4 hours
9. custommost of the MeOH was removed in vacuo
10. extractionthe mixture was extracted with EtOAc (×3)
11. washThe combined organic layers were washed, (H2O, brine),
12. dry with materialdried (Na2SO4)
13. customevaporated
14. customThe residue was purified by flash chromatography (SiO2/hexane-EtOAc, 4:1)