盐酸托莫西汀.doc

Atomoxetine hydrochloride, Tomoxetine hydrochloride, LY-1396--药物合成数据库 发布时间：2004-10-25 来源：本站整理 【药物名称】 Atomoxetine hydrochloride, Tomoxetine hydrochloride, LY-139602 [(+)-isomer], LY-135252(racemate), LY-139603, Strattera 【化学名】 (R)-(-)-N-Methyl-gamma-(2-methylphenoxy)benzenepropanamine hydrochloride; (R)-(-)-N-Methyl-3-phenyl-3-(2-methylphenoxy)propylamine hydrochloride 【CAS登记号】 82248-59-7, 83015-26-3 (free base) 【结构式】 【分子式】 C17-H21-N-O.Cl-H 【分子量】 291.8198 【原研厂家】 Lilly (Originator) 【作用类别】 Antidepressants, Attention Deficit Hyperactivity Disorder (ADHD), Treatment of, Autism, Treatment of, Mood Disorders, Treatment of, PSYCHOPHARMACOLOGIC DRUGS, Norepinephrine Reuptake Inhibitors 【研发状态】 Launched-2003 【合成情况】 　 〖来源〗 Tetrahedron Lett 〖合成路线〗 〖标题〗 A new chemoenzymatic enantioselective synthesis of R-(-)-tomoxetine, (R)-fluoxetine and (S)-fluoxetine 〖合成方法〗 A new synthesis for tomoxetine hydrochloride has been reported: The reduction of benzoylacetic acid ethyl ester (I) with Bakers yeast and glucose in water, or the enzymatic hydrolysis of 3-acetoxy-3-phenylpropionic acid ethyl ester (II), gives (-)-3-hydroxy-3-phenylpropionic acid ethyl ester (III), which by reaction with methylamine yields the corresponding amide (IV). The reduction of (IV) with LiAlH4 in ether affords (-)-3-hydroxy-N-methyl-3-phenylpropylamine (V), which is protected with di-tert-butyldicarbonate to the amide (VI). The condensation of (VI) with o-cresol (VII) by means of triphenylphosphine and diethylazodicarboxylate (DEAD) in ether yields the protected final product (VIII), which is finally deprotected with dry HCl in methanol. 〖作者〗 Dike, S.Y.; Kumar, A.; Ner, D.H. 〖参考〗 Dike, S.Y.; Kumar, A.; Ner, D.H.; A new chemoenzymatic enantioselective synthesis of R-(-)-tomoxetine, (R)-fluoxetine and (S)-fluoxetine. Tetrahedron Lett 1991, 32, 16, 1901 〖出处〗 Tetrahedron Lett1991,32,(16):1901 〖备注〗 A new synthesis for tomoxetine hydrochloride has been reported: The reduction of benzoylacetic acid ethyl ester (I) with