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合成6-氟-4-氧代苯并吡喃-2-羧酸(1)在乙酸中以Pd/C催化氢化得6-氟-3,4-二氢-2H-苯并吡喃-2-羧酸(Ⅱ),进一步用双(2-甲基丙基)氢化铝和1,1’-羰基双(1H-咪唑)在THF中还原得到6-氟-3,4-二氢-2H-苯并吡喃-2-甲醛(Ⅲ),Ⅲ与三甲基亚砜碘化物和NaH在DMSO中反应得到2-环氧乙基-3,4-二氢-2H-苯并吡喃(Ⅳ),Ⅳ与苄胺(Ⅴ)在醇中回流缩合得到Ⅵ,后者在甲醇中用Pd/C催化氢化脱去保护基得到Nebivolol[AU 8436326,EP 145067,JP 85132977]。
Synthesis of 6-fluoro-4-oxochromen-2-carboxylic acid (1) Pd / C-catalyzed hydrogenation in acetic acid gave 6-fluoro-3,4-dihydro-2H-benzopyran-2 -carboxylic acid (II) which is further reduced with bis (2-methylpropyl) aluminum hydride and 1,1’-carbonylbis (1H-imidazole) in THF to give 6-fluoro-3,4-dihydro-2H -benzopyran-2-carbaldehyde (III), III with trimethylsulfoxide iodide and NaH in DMSO to give 2-oxiranyl-3,4-dihydro-2H-benzopyran ( (IV) with benzylamine (V) by reflux condensation in alcohol to afford VI, which is deprotected by Pd / C catalytic hydrogenation in methanol to give Nebivolol [AU 8436326, EP 145067, JP 85132977].