Nisoxetine

尼索西汀Chemical Name: (?-3-(2-Methoxyphenoxy)-N-methyl-3-phenyl-1-propanamine
CAS No. 53179-07-0
项目整合开发状态: Not Determined
项目研究机构: Lilly (Originator)
合成路线:A new synthesis of tomoxetine has been described: The reduction of omega-chloropropiophenone (I) with NaBH4 in ethanol gives 3-chloro-1-phenyl-1-propanol (II),which is treated with butyric anhydride and pyridine in dichloromethane to yield the corresponding racemic ester (III).The optical resolution of (III) with immobilized lipase B from Candida antarctica (CALB) affords a mixture of unreacted (S)-ester and (R)-alcohol (IV) that are separated by column chromatography.Condensation of th (R)-alcohol (IV) with 2-methylphenol (V) by means of PPh3 and diethyl azodicarboxylate (DEAD) in THF gives the corresponding ether (VI),which is finally treated with methylamine in refluxing ethanol.

合成路线:The reduction of omega-chloropropiophenone (I) with NaBH4 in ethanol gives 3-chloro-1-phenyl-1-propanol (II),which is treated with butyric anhydride and pyridine in dichloromethane,yielding the corresponding racemic ester (III).The optical resolution of (III) with immobilized lipase B from Candida antarctica (CALB) affords a mixture of unreacted (S)-ester and (R)-alcohol (IV),which are separated by column chromatography.The condensation of alcohol (IV) with 4-(trifluoromethyl)phenol (V) by means of PPh3 and diethyl azodicarboxylate (DEAD) in THF gives the corresponding ether (VI),which is finally treated with methylamine in refluxing ethanol.

合成路线:The reduction of omega-chloropropiophenone (I) with NaBH4 in ethanol gives 3-chloro-1-phenyl-1-propanol (II),which is treated with butyric anhydride and pyridine in dichloromethane yielding the corresponding racemic ester (III).The optical resolution of (III) with immobilized lipase B from Candida antarctica (CALB) affords a mixture of unreacted (S)-ester and (R)-alcohol (IV) that are separated by column chromatography.The condensation of alcohol (IV) with 2-methoxyphenol (V) by means of PPh3 and diethyl azodicarboxylate (DEAD) in THF gives the corresponding ether (VI),which is finally treated with methylamine in refluxing ethanol.