新产品编号:359623

Chemical Name: 2-[5-[2(E)-(N,N-Diethylcarbamoyl)-1-methylvinyl]-2-(2,6-difluorobenzyloxy)phenoxy]acetic acid
CAS No. 205317-49-3
项目整合开发状态: Preclinical
项目研究机构: Novartis (Originator)
合成路线:3',4'-Dihydroxyacetophenone (I) was selectively alkylated at position 4' with alpha-bromo-2,6-difluorotoluene (II) in the presence of Li2CO3 in DMF.The resulting ether (III) was further alkylated with ethyl bromoacetate (IV) to give (V).Subsequent Horner-Emmons condensation of (V) with the phosphonoacetamide (VI) provided cinnamide (VII).The target carboxylic acid was then obtained by saponification of the ethyl ester of (VII) with NaOH.

合成路线:Simultaneous bromination and esterification of 2'-hydroxyphenylacetic acid (I) using tetrabutylammonium tribromide in EtOH at r.t.afforded (II),which was O-alkylated with alpha-bromo-2,6-difluorotoluene (III) in the presence of K2CO3 in refluxing acetone to yield ether (IV).Subsequent Heck olefination of (IV) with diethyl crotonamide (V) in the presence of palladium acetate and tri-o-tolylphosphine provided cinnamide (VI).The target carboxylic acid was then obtained by saponification of the ethyl ester of (VI) with NaOH.