Nafoxidine hydrochloride
Chemical Name: 1-[2-[4-(6-Methoxy-2-phenyl-3,4-dihydronaphthalen-1-yl)phenoxy]ethyl]pyrrolidine hydrochloride
项目整合开发状态: Not Determined
项目研究机构: Pfizer (Originator)
合成路线:The condensation of 3-methoxyacetophenone (I) with benzaldehyde (II) by means of NaOH in ethanol - water gives 3'-methoxychalcone (III),which by addition of HCN (KCN) in ethanol-acetic acid is transformed into 2-phenyl-4-(3-methoxyphenyl)-4-oxobutyronitrile (IV).The hydrolysis of (IV) with aqueous H2SO4 at 100 C affords the corresponding ketoacid (V),which is reduced with amalgamated zinc and 2N HCl yielding 2-phenyl-4-(3-methoxyphenyl)butyric acid (VI).The cyclization of (VI) by means of liquid HF yields 2-phenyl-6-methoxy-1,2,3,4-tetrahydro-1-naphthalenone (VII),which is finally condensed with 4-(2-pyrrolidinoethoxy)phenylmagnesium bromide in refluxing THF.
📌 参考资料/链接：
参考文献标题:Nafoxidine
文献作者:Thorpe,P.; Casta馿r,J.
参考来源:Drugs Fut 1978,3(3),211
📄 详细内容
合成路线:The condensation of 3-methoxyacetophenone (I) with benzaldehyde (II) by means of NaOH in ethanol - water gives 3'-methoxychalcone (III),which by addition of HCN (KCN) in ethanol-acetic acid is transformed into 2-phenyl-4-(3-methoxyphenyl)-4-oxobutyronitrile (IV).The hydrolysis of (IV) with aqueous H2SO4 at 100 C affords the corresponding ketoacid (V),which is reduced with amalgamated zinc and 2N HCl yielding 2-phenyl-4-(3-methoxyphenyl)butyric acid (VI).The cyclization of (VI) by means of liquid HF yields 2-phenyl-6-methoxy-1,2,3,4-tetrahydro-1-naphthalenone (VII),which is finally condensed with 4-(2-pyrrolidinoethoxy)phenylmagnesium bromide in refluxing THF.
参考文献标题:
文献作者:Lednicer,D.
参考来源:US 3274213
合成路线:The condensation of 3-methoxyacetophenone (I) with benzaldehyde (II) by means of NaOH in ethanol - water gives 3'-methoxychalcone (III),which by addition of HCN (KCN) in ethanol-acetic acid is transformed into 2-phenyl-4-(3-methoxyphenyl)-4-oxobutyronitrile (IV).The hydrolysis of (IV) with aqueous H2SO4 at 100 C affords the corresponding ketoacid (V),which is reduced with amalgamated zinc and 2N HCl yielding 2-phenyl-4-(3-methoxyphenyl)butyric acid (VI).The cyclization of (VI) by means of liquid HF yields 2-phenyl-6-methoxy-1,2,3,4-tetrahydro-1-naphthalenone (VII),which is finally condensed with 4-(2-pyrrolidinoethoxy)phenylmagnesium bromide in refluxing THF.
参考文献标题:
文献作者:Duncan,G.W.; Lednicer,D.
参考来源:US 3483293