Potassium Hydroxide → Irbesartan

Participants

Reaction Conditions

Reaction Steps

16.4 g of sodium hydroxide dissolved in 240 ml of purified water was added to the mixture of 5-(4′-bromomethyl-biphenyl-2-yl)-1-trityl-1H-tetrazole (59.5 g) and 2n-butyl-1,3-diazaspiro (4,4) non-1-en-4-one HCl (25 g) and tetra butyl ammonium bromide (2.15 g) in toluene (250 ml). The mixture was heated to about 85° C. for about 2 hours. After reaction completion, the reaction mass was cooled to about 25° C. and the toluene layer separated. The aqueous phase was extracted with toluene (105 ml). The combined organic layer was evaporated. The residue was dissolved in acetone (208 ml) and 3N HCl was added (600 ml). The contents were stirred at room temperature until reaction completion (as monitored by TLC). After reaction completion, a solution of KOH (30.4 g) in water (208 ml) was slowly added and acetone was evaporated under reduced pressure. The precipitated trityl alcohol was filtered and washed with water (2×105 ml). The filtrate was washed with toluene and slowly acidified to pH 4 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 (2×50 ml) and dried under reduced pressure at 50-60° C. to yield irbesartan free base (92.0%).

Provenance & Evidence