反应详情

To a suspension of N-{4-[3-(4-fluoro-benzenesulfonyl)-4-hydroxy-phenoxy]-3,5-dimethyl-phenyl}-malonamic acid methyl ester (7.14 g, 14.6 mmol) in 50% aqueous methanol (56 mL) was added a 5 M solution of potassium hydroxide (8.8 mL, 44 mmol) to give a reddish-brown solution. The solution was stirred at RT for 45 min then diluted with water (200 mL). The solution was washed with EtOAc (3×50 ml) and the combined washings were extracted with 0.1 M KOH (50 mL). The combined basic aqueous solutions were acidified with concentrated HCl and extracted with EtOAc (3×50 mL). The combined extracts were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated to a dark amber oil. The oil was dissolved in EtOAc (20 mL) and cyclohexane (100 mL) was added to give an oil, which slowly solidified on stirring at RT. The suspension was stirred 64 h at RT, then filtered. The solid was washed with cyclohexane (3×50 mL) and dried to give the title compound of Step F and Example 4-2 (6.26 g) as a solid. MS (APCl+) Calc.: 473.1. Found: 474.3 (M+1).

1. customto give a reddish-brown solution
2. washThe solution was washed with EtOAc (3×50 ml)
3. extractionthe combined washings were extracted with 0.1 M KOH (50 mL)
4. extractionextracted with EtOAc (3×50 mL)
5. washThe combined extracts were washed with brine
6. dry with materialdried over anhydrous sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated to a dark amber oil
9. dissolutionThe oil was dissolved in EtOAc (20 mL)
10. additioncyclohexane (100 mL) was added
11. customto give an oil, which
12. stirringon stirring at RT
13. stirringThe suspension was stirred 64 h at RT
14. filtrationfiltered
15. washThe solid was washed with cyclohexane (3×50 mL)
16. customdried