Hydrochloric Acid → Losartan

Participants

Reaction Conditions

Reaction Steps

In the last step, trityl losartan was suspended in methanol and cooled to ˜10° C. 3.4 N Hydrochloric acid was added to the slurry. After a period of time, the pH of the reaction mixture was raised to 13 with 10 N NaOH. Methanol was then distilled off while makeup water was added. After distillation, additional water and toluene were added. The toluene phase was separated and the aqueous phase was extracted once more with toluene. Ethyl acetate and acetic acid were then added to the aqueous phase. Losartan was recovered from the aqueous phase as a solid and further purified by slurrying in ethyl acetate. Losartan was obtained in 88.5% yield and 98.8% purity as determined by HPLC. This process is also described in U.S. Pat. Nos. 5,128,355 and 5,155,188.

Provenance & Evidence