Butopamine, LY-131126
布托巴胺Chemical Name: 4-[3(R)-[2(R)-Hydroxy-2-(4-hydroxyphenyl)ethylamino]butyl]phenol
CAS No. 66734-12-1
项目整合开发状态: Biological Testing
项目研究机构:
合成路线:The benzylation of methyl 2-(4-hydroxyphenyl)ethyl ketone (I),with benzyl chloride and NaOH gives methyl 2-(4-benzyloxyphenyl)ethyl ketone (II),which is reductocondensed with NH3 by means of H2 over Raney-Ni in ethanol yielding 1-methyl-3-(4-benzyloxyphenyl)propylamine (III).The optical resolution of (III) with R-mandeli acid affords the R-isomer (IV),which is acetylated with R-2-(4-benzyloxyphenyl)-2-hydroxyacetic acid (V) by means of 1-hydroxybenzotriazole and dicyclohexylcarbodiimide in DMF to R,R-N-[2-(4-benzyloxyphenyl)-2-hydroxy-1-oxoethyl]-1-methyl-3-(4-benzyloxyphenyl)propylamine (VI).The reduction of (VI) with borane - dimethyl sulfide complex in THF gives R,R-N-[2-(4-benzyloxyphenyl)-2-hydroxyethyl]-1-methyl-3-(4-benzyloxyphenyl)propylamine (VII),which is finally debenzylated by hydrogenolysis with H2 over Raney-Ni in ethanol.
📌 参考资料/链接：
参考文献标题:
文献作者:Mills,J.; et al.
参考来源:BE 877391; EP 7205; FR 2430408; GB 2029407; JP 8009098
📄 详细内容
合成路线:The benzylation of methyl 2-(4-hydroxyphenyl)ethyl ketone (I),with benzyl chloride and NaOH gives methyl 2-(4-benzyloxyphenyl)ethyl ketone (II),which is reductocondensed with NH3 by means of H2 over Raney-Ni in ethanol yielding 1-methyl-3-(4-benzyloxyphenyl)propylamine (III).The optical resolution of (III) with R-mandeli acid affords the R-isomer (IV),which is acetylated with R-2-(4-benzyloxyphenyl)-2-hydroxyacetic acid (V) by means of 1-hydroxybenzotriazole and dicyclohexylcarbodiimide in DMF to R,R-N-[2-(4-benzyloxyphenyl)-2-hydroxy-1-oxoethyl]-1-methyl-3-(4-benzyloxyphenyl)propylamine (VI).The reduction of (VI) with borane - dimethyl sulfide complex in THF gives R,R-N-[2-(4-benzyloxyphenyl)-2-hydroxyethyl]-1-methyl-3-(4-benzyloxyphenyl)propylamine (VII),which is finally debenzylated by hydrogenolysis with H2 over Raney-Ni in ethanol.
参考文献标题:Butopamine
文献作者:Blancafort,P.; Serradell,M.N.; Castar,J.; Thorpe,P.J.
参考来源:Drugs Fut 1981,6(6),340
产品链接: CAS No. 66734-12-1››