反应详情

A mixture of the title product of Step (D) (350 mg; 0.59 mmol), 6N HCl (6 ml) and EtOH (6 ml) was refluxed for 3 hours. After cooling, the reaction mixture was partitioned between EtOAc (50 ml) and water (25 ml). The aqueous layer was extracted with EtOAc (50 ml) and the combined organic layers were washed with brine (2×50 ml). The blue solution was dried (MgSO4) and concentrated to a dark blue residue. Attempts at purifying this residue using silica gel chromatography were unsuccessful. The material isolated from combining all fractions was subjected to reverse phase preparative HPLC. (30×500 mm ODS column; S-3; two injections-30 and 150 mg; stepwise gradient 75-83% MeOH/H2O+0.1% trifluoroacetic acid (TFA); 2% increments every 5 minutes; 35 ml/minute flow rate.) The pure fractions were concentrated and the residues were partitioned between EtOAc and water. The organic layer was washed with water and brine. Drying (MgSO4), concentration and co-evaporation from MeOH/H2O afforded 130 mg (43%) of the title product of this Example as a light yellow amorphous solid. mp 85-95° C. (dec.); Rf=0.63, EtOAc (UV detection).

1. temperaturewas refluxed for 3 hours
2. temperatureAfter cooling
3. customthe reaction mixture was partitioned between EtOAc (50 ml) and water (25 ml)
4. extractionThe aqueous layer was extracted with EtOAc (50 ml)
5. washthe combined organic layers were washed with brine (2×50 ml)
6. dry with materialThe blue solution was dried (MgSO4)
7. concentrationconcentrated to a dark blue residue
8. customAttempts at purifying this residue
9. customThe material isolated
10. customevery 5 minutes
11. concentration) The pure fractions were concentrated
12. customthe residues were partitioned between EtOAc and water
13. washThe organic layer was washed with water and brine
14. customDrying
15. concentration(MgSO4), concentration and co-evaporation from MeOH/H2O