反应详情

A solution of 1-(3-bromo-phenoxy)-4-chloro-2-phenoxy-benzene (0.15 g, 0.4 mmol), (4-hydroxy-2-methyl-phenylsulfanyl)-acetic acid ethyl ester (99 mg, 0.44 mmol), copper(I) chloride (20 mg, 0.2 mmol), 2,2,6,6-tetramethyl-3,5-heptanedione (0.02 mL, 0.1 mmol), and cesium carbonate (156 mg, 0.48 mmol) in NMP (3 mL) is heated to 120° C. The reaction is stirred overnight and cooled to rt. The reaction is quenched with 1N aqueous HCl and extracted with ethyl ether. The organic is washed with brine, dried over sodium sulfate, and filtered. The solvent is removed to afford the crude ester intermediate. The intermediate is treated with 5N NaOH (0.4 mL, 2.2 mmol) in MeOH (5 mL) and heated to reflux. The reaction is stirred at reflux for 2 hours and then cooled. The reaction is quenched with 1N aqueous HCl to give pH=4. The aqueous layer is extracted with ethyl ether. The organic layer is washed with brine, dried over sodium sulfate, and filtered. The solvent is removed to afford the crude product. The crude is purified by prep HPLC to afford 78 mg (40%) of desired product. 1H NMR (400 MHz, CDCl3); MS (ES+) m/z mass calculated for C27H21ClO5S 492, found 493 and 495 (M+1 and M+3, 100%).

1. customThe reaction is quenched with 1N aqueous HCl
2. extractionextracted with ethyl ether
3. washThe organic is washed with brine
4. dry with materialdried over sodium sulfate
5. filtrationfiltered
6. customThe solvent is removed
7. customto afford the crude ester intermediate
8. temperatureheated to reflux
9. stirringThe reaction is stirred
10. temperatureat reflux for 2 hours
11. temperaturecooled
12. customThe reaction is quenched with 1N aqueous HCl
13. customto give pH=4
14. extractionThe aqueous layer is extracted with ethyl ether
15. washThe organic layer is washed with brine
16. dry with materialdried over sodium sulfate
17. filtrationfiltered
18. customThe solvent is removed
19. customto afford the crude product
20. customThe crude is purified by prep HPLC