反应详情

To a stirred solution of 0.84 g of 4-[4-(3-benzyloxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-fluoro-benzonitrile in 5 mL of tetrahydrofuran and 5.6 mL of methanol were added 1.14 g of hydroxylamine hydrochloride followed by 1.8 mL of triethylamine. The reaction mixture was stirred at reflux temperature for 2 h and then at room temperature overnight. The reaction mixture was refluxed for an additional 2 h and then concentrated under reduced pressure. The residue was taken up into dichloromethane then water was added. The aqueous layer was separated and extracted three times with dichloromethane. The combined organic layers were washed with water, dried over magnesium sulfate, filtered and concentrated under reduced pressure to give 0.840 g of crude product as a yellow gum. Precipitation in heptane afforded 620 mg of 4-[4-(3-benzyloxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-fluoro-N-hydroxy-benzamidine as a beige powder.

1. temperatureat reflux temperature for 2 h
2. customat room temperature
3. customovernight
4. temperatureThe reaction mixture was refluxed for an additional 2 h
5. concentrationconcentrated under reduced pressure
6. additionwater was added
7. customThe aqueous layer was separated
8. extractionextracted three times with dichloromethane
9. washThe combined organic layers were washed with water
10. dry with materialdried over magnesium sulfate
11. filtrationfiltered
12. concentrationconcentrated under reduced pressure
13. customto give 0.840 g of crude product as a yellow gum
14. customPrecipitation in heptane