当前位置: 首页 » 资料 » 医药中间体库 » 96854-34-1,C9H12O2,152.1948,(S)-1-Phenyl-1,3-propanediol; (S

96854-34-1,C9H12O2,152.1948,(S)-1-Phenyl-1,3-propanediol; (S

放大字体  缩小字体 更新日期:2018-11-23  浏览次数:106
摘 要:96854-34-1,C9H12O2,152.1948,(S)-1-Phenyl-1,3-propanediol; (S)-3-Phenyl-1,3-propanediol
  • 【化学名】(S)-1-Phenyl-1,3-propanediol; (S)-3-Phenyl-1,3-propanediol
  • 【CAS登记号】96854-34-1
  • 【结构式】96854-34-1,C9H12O2,152.1948,(S)-1-Phenyl-1,3-propanediol; (S--药物合成数据库
  • 【分子式】C9H12O2
  • 【分子量】152.1948
  • 【来源】Acros Organics; Kaneka Corporation - Fine Chemicals Division
  • 【合成情况】 
  • 〖目标产物〗Atomoxetine hydrochloride, Tomoxetine hydrochloride, LY-139602 [(+)-isomer], LY-135252(racemate), LY-139603, Strattera
  • 〖合成路线〗
  • 〖合成方法〗The asymmetric epoxidation of (E)-3-phenyl-2-propen-1-ol (I) by means of titanium tetraisopropoxide, (+)-diethyl tartrate (+)-(DET) and tBu-OOH in dichloromethane gives the chiral epoxide (II), which is opened by means of bis(2-methoxyethoxy)aluminum hydride (Red-Al) in DME to yield the chiral diol (III). The regioselective reaction of (III) with Ms-Cl and TEA in ethyl ether affords the primary mesylate (IV), which is condensed with 2-methylphenol (V) by means of PPh3 and DEAD in ethyl ether to provide the adduct (VI). Finally this compound is treated with methylamine in hot aq. THF to give rise to the target (R)-tomoxetine.
  • 〖参考〗Gao, Y.; Sharpless, K.B.; Asymmetric synthesis of both enantiomers of tomoxetine and fluoxetine. Selective reduction of 2,3-epoxycinnamyl alcohol with Red-Al. J Org Chem 1988, 53, 17, 4081
  • 〖目标产物〗Atomoxetine hydrochloride, Tomoxetine hydrochloride, LY-139602 [(+)-isomer], LY-135252(racemate), LY-139603, Strattera
  • 〖合成路线〗
  • 〖合成方法〗The asymmetric epoxidation of (E)-3-phenyl-2-propen-1-ol (I) by means of titanium tetraisopropoxide, (+)-diethyl tartrate (+)-(DET) and tBu-OOH in dichloromethane gives the chiral epoxide (II), which is opened by means of bis(2-methoxyethoxy)aluminum hydride (Red-Al) in DME to yield the chiral diol (III). The regioselective reaction of (III) with Ms-Cl and TEA in ethyl ether affords the primary mesylate (IV), which is condensed with 2-methylphenol (V) by means of PPh3 and DEAD in ethyl ether to provide the adduct (VI). Finally this compound is treated with methylamine in hot aq. THF to give rise to the target (R)-tomoxetine.
  • 〖参考〗Gao, Y.; et al.; Catalytic asymmetric epoxidation and kinetic resolution: Modified procedures including in situ derivatization. J Am Chem Soc 1987, 109, 19, 5765
  • 〖目标产物〗(S)-Fluoxetine
  • 〖合成路线〗
  • 〖合成方法〗The reduction of 3-hydroxy-3-phenylpropionic acid ethyl ester (I) with LiAlH4 in THF gives 1-phenylpropane-1,3-diol (II), which is treated with Ts-Cl and TEA in dichloromethane to yield the monotosylate (III). The optical resolution of (III) by means of (Pd(OAc)2, (-)-sparteine and O2 in hot toluene yields a mixture of the desired (S)-1-phenyl-3-(tosyloxy)-1-propanol (IV) and the propiophenone (V) that is separated by column chromatography. The reaction of (IV) with methylamine in hot THF affords the chiral secondary amine (VI), which is finally condensed with 4-(trifluoromethyl)chlorobenzene (VII) by means of NaH in hot dimethylacetamide to provide the target (S)-fluoxetine.
  • 〖参考〗Ali, I.S.; Sudalai, A.; Pd-catalyzed kinetic resolution of benzylic alcohols: A practical synthesis of (R)-tomoxetine and (S)-fluoxetine hydrochlorides. Tetrahedron Lett 2002, 43, 31, 5435
 
本文导航:
  • (1) 96854-34-1,C9H12O2,152.1948,(S)-1-Phenyl-1,3-propanediol; (S
  • 下一篇:鳖甲
  • 上一篇:暂无
 
[ 资料搜索 ]  [ 加入收藏 ]  [ 告诉好友 ]  [ 打印本文 ]  [ 关闭窗口 ]

 

 
推荐图文
推荐资料
热门关注