反应详情

An aqueous solution (300 mL) of phenyl glycine methyl ester-HCl (100 g) was neutralized to pH 8 with 10N NaOH. The aqueous solution was extracted with EtOAc (3×200 mL). The combined organic extracts were dried over MgSO4, filtered, and concentrated. The residue (56.7 g, 344 mmol) was dissolved in trimethylorthoformate (100 mL) and treated with benzaldehyde (34.9 mL, 36.4 g, 344 mmol). After stirring for 2 h, the reaction was diluted with Et2O (200 mL) and washed with water (3×50 mL). The organic solution was dried over MgSO4, filtered, and concentrated. A portion of the imine residue (26.8 g, 100 mmol) was dissolved in dichloromethane (240 mL) and treated with 160 mL of 10N NaOH, methallyl dichloride (50.0 g, 400 mmol), and Bu4NHSO4 (3.59 g). After stirring for 10 h at rt, the reaction was diluted with dichloromethane and the organic solution separated, dried over MgSO4, filtered, and concentrated. The residue was redissolved in Et2O/1N HCl (200 mL/200 mL) and stirred for 2 h. The aqueous phase was separated and neutralized with iON NaOH (to pH 8). The aqueous mixture was extracted with EtOAc (3×200 mL). The combined organic solutions were dried over MgSO4, filtered and concentrated. The residue was dissolved in water and neutralized (to pH 8). Extraction of this mixture with EtOAc (X 3) followed by drying over MgSO4, filtratration, and concentration provided crude 1B-2. Purification of this residue by flash chromatography (SiO2; 30% EtOAc/hexanes) provided pure 1B-2.

1. extractionThe aqueous solution was extracted with EtOAc (3×200 mL)
2. dry with materialThe combined organic extracts were dried over MgSO4
3. filtrationfiltered
4. concentrationconcentrated
5. washwashed with water (3×50 mL)
6. dry with materialThe organic solution was dried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated
9. stirringAfter stirring for 10 h at rt
10. customthe organic solution separated
11. dry with materialdried over MgSO4
12. filtrationfiltered
13. concentrationconcentrated
14. dissolutionThe residue was redissolved in Et2O/1N HCl (200 mL/200 mL)
15. stirringstirred for 2 h
16. customThe aqueous phase was separated
17. extractionThe aqueous mixture was extracted with EtOAc (3×200 mL)
18. dry with materialThe combined organic solutions were dried over MgSO4
19. filtrationfiltered
20. concentrationconcentrated
21. dissolutionThe residue was dissolved in water
22. extractionExtraction of this mixture with EtOAc (X 3)
23. dry with materialby drying over MgSO4, filtratration, and concentration
24. customprovided crude 1B-2
25. customPurification of this residue by flash chromatography (SiO2; 30% EtOAc/hexanes)
26. customprovided pure 1B-2