反应详情

温度

0 °C

Water (10 L) was added to a 22 L 4-neck round bottom flask. The water was cooled to 0° C. At 0° C., potassium hydroxide (855 g, 15.24 mol) was added followed by losartan potassium (500 g, 1.09 mol)), sodium periodate (554 g, 2.59 mol) and ruthenium (III) chloride hydrate (12 g, 0.05 mol) and the reaction mixture was stirred at 0° C. overnight. The reaction mixture was filtered. IPA (90 mL) was added to the filtrate while stirring. The solution was warmed to 25° C. and stirred for 2.5 hrs. After 2.5 hrs., phosphoric acid (1200 mL) was added, maintaining the temperature below +30° C. The mixture was stirred for 30 min and the product was filtered, washing with water. The residue was dried in the vacuum oven at 55° C. overnight. The solid was dissolved in methanol (4 L) and isopropyl acetate (12 L), and charcoal (activated carbon) (100 g) was added. The mixture was stirred at rt for 3.5 hrs, filtered and concentrated. The product was redissolved in DCM/MeOH and precipitated with heptane to afford the title compound as a greenish/brown foam which was used in subsequent steps without further purification.

1. filtrationThe reaction mixture was filtered
2. additionIPA (90 mL) was added to the filtrate
3. stirringwhile stirring
4. temperatureThe solution was warmed to 25° C.
5. stirringstirred for 2.5 hrs
6. waitAfter 2.5 hrs
7. addition, phosphoric acid (1200 mL) was added
8. temperaturemaintaining the temperature below +30° C
9. stirringThe mixture was stirred for 30 min
10. filtrationthe product was filtered
11. washwashing with water
12. customThe residue was dried in the vacuum oven at 55° C. overnight
13. dissolutionThe solid was dissolved in methanol (4 L)
14. additionisopropyl acetate (12 L), and charcoal (activated carbon) (100 g) was added
15. stirringThe mixture was stirred at rt for 3.5 hrs
16. filtrationfiltered
17. concentrationconcentrated
18. dissolutionThe product was redissolved in DCM/MeOH
19. customprecipitated with heptane