title: Novel Syntheses of 2-Butyl-5-chloro-3H-imidazole-4-carbaldehyde: A Key Intermediate for the Synthesis of the Angiotensin II Antagonist Losartan.
abstract: Reaction of glycine methyl ester (19) with imidate 18 under carefully optimized conditions allowed preparation of the rather unstable imidazolinone 11 in ca. 90% yield. Reaction of 11 with POCl(3)/DMF followed by aqueous workup gave aldehyde 2, a key intermediate for the synthesis of the angiotensin II antagonist Losartan, in ca. 55% yield. Structural identification of intermediates and byproducts formed during both the reaction to prepare 11 and the reaction of 11 with POCl(3)/DMF allowed development of several closely related syntheses of aldehyde 2.
authors.affiliation: Cerecon AG, Hauptstrasse 144, CH-4416, Bubendorf, Switzerland.
authors.forename: Gareth J.
authors.initials: GJ
authors.lastname: Griffiths
authors.forename: Michael B.
authors.initials: MB
authors.lastname: Hauck
authors.forename: René
authors.initials: R
authors.lastname: Imwinkelried
authors.forename: Jörg
authors.initials: J
authors.lastname: Kohr
authors.forename: Conrad A.
authors.initials: CA
authors.lastname: Roten
authors.forename: Gerhard C.
authors.initials: GC
authors.lastname: Stucky
authors.forename: Jacques
authors.initials: J
authors.lastname: Gosteli