反应详情

温度

90 °C

5-(4′-bromomethyl-biphenyl-2-yl)-1-trityl-1H-tetrazole (24.6 g) was charged to toluene (240 ml). To this, a solution of KOH (10.4 g), 2n-butyl-1,3-diazaspiro (4,4) non-1-en-4 one HCl (12.0 g) and Bu4NHSO4 (1.8 g) in water (40 ml) was added. The two-phase mixture was then heated to 90° C. for 90 minutes under vigorous stirring. The reaction mixture was cooled to room temperature. The toluene layer was separated and the aqueous phase was extracted with toluene (50 ml). The combined organic layer was evaporated. The residue was dissolved in acetone (100 ml) and 3N HCl (52 ml) and stirred at room temperature (TLC monitoring). A solution of KOH (14.6 g) in water (100 ml) was slowly added and acetone was evaporated under reduced pressure. The precipitated trityl alcohol was filtered and washed with water (2×50 ml). The filtrate was washed with toluene and slowly acidified to pH 4.0 with 3 N HCl. The suspension was cooled to 0-4° C., stirred for an additional 30 minutes and filtered. The cake was washed with cold isopropanol (2×25 ml) and dried under reduced pressure at 50-60° C. to yield irbesartan free base (84%).

1. temperatureThe reaction mixture was cooled to room temperature
2. customThe toluene layer was separated
3. extractionthe aqueous phase was extracted with toluene (50 ml)
4. customThe combined organic layer was evaporated
5. dissolutionThe residue was dissolved in acetone (100 ml)
6. additionA solution of KOH (14.6 g) in water (100 ml) was slowly added
7. customacetone was evaporated under reduced pressure
8. filtrationThe precipitated trityl alcohol was filtered
9. washwashed with water (2×50 ml)
10. washThe filtrate was washed with toluene
11. temperatureThe suspension was cooled to 0-4° C.
12. stirringstirred for an additional 30 minutes
13. filtrationfiltered
14. washThe cake was washed with cold isopropanol (2×25 ml)
15. customdried under reduced pressure at 50-60° C.