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ent-帕罗醇 | 389573-45-9

中文名称
ent-帕罗醇
中文别名
——
英文名称
(-)-trans-4-(4'-Fluorophenyl)-3-hydroxymethyl-N-methyl-piperidine
英文别名
(3R,4S)-trans-4-(4-fluorophenyl)-3-hydroxymethyl-1-methylpiperidine;(+)-trans-4-(4-fluorophenyl)-3-hydroxymethyl-1-methylpiperidine;(3R,4S)-4-(4-fluorophenyl)-3-hydroxymethyl-1-methylpiperidine;((3R,4S)-4-(4-fluorophenyl)-1-methylpiperidin-3-yl)methanol;trans-4-(4-fluorophenyl)-3-hydroxymethyl-1-methylpiperidine;(3R,4S)-paroxol;[(3R,4S)-4-(4-fluorophenyl)-1-methylpiperidin-3-yl]methanol
ent-帕罗醇化学式
CAS
389573-45-9
化学式
C13H18FNO
mdl
——
分子量
223.29
InChiKey
CXRHUYYZISIIMT-DGCLKSJQSA-N
BEILSTEIN
——
EINECS
——
  • 物化性质
  • 计算性质
  • ADMET
  • 安全信息
  • SDS
  • 制备方法与用途
  • 上下游信息
  • 反应信息
  • 文献信息
  • 表征谱图
  • 同类化合物
  • 相关功能分类
  • 相关结构分类

物化性质

  • 熔点:
    98-100°C
  • 沸点:
    300.3±42.0 °C(Predicted)
  • 密度:
    1.092±0.06 g/cm3(Predicted)
  • 溶解度:
    可溶于丙酮(少许)、氯仿(少许)、DMSO(少许)

计算性质

  • 辛醇/水分配系数(LogP):
    1.8
  • 重原子数:
    16
  • 可旋转键数:
    2
  • 环数:
    2.0
  • sp3杂化的碳原子比例:
    0.54
  • 拓扑面积:
    23.5
  • 氢给体数:
    1
  • 氢受体数:
    3

SDS

SDS:6e905a57e3cd8c9972adca44a772e1fb
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上下游信息

  • 上游原料
    中文名称 英文名称 CAS号 化学式 分子量
  • 下游产品
    中文名称 英文名称 CAS号 化学式 分子量

反应信息

  • 作为反应物:
    参考文献:
    名称:
    反式-4-(4-氟苯基)-3-氯甲基-1-甲基哌啶在氧化铝上的微波辅助消除反应
    摘要:
    摘要 在无溶剂条件和微波照射下,反式-4-(4-氟苯基)-3-氯甲基-1-甲基哌啶3b在氧化铝或KF-氧化铝上发生消除反应。与在有机碱存在下加热的“经典”方法相比,微波辅助方法可提供更高产率的 4-(4-氟苯基)-3-亚甲基-1-甲基哌啶 7b (65.5-71%)更短的反应时间(20-40 分钟)。此外,7b 中的环外双键重排为环内双键,得到化合物 8。研究了氧化铝和辐照时间对反应转化率和异构化程度的影响。
    DOI:
    10.1081/scc-120037925
  • 作为产物:
    描述:
    (3R, 4S)-trans-3-carbomethoxy-4-(4-fluorophenyl)-N-methyl-piperidine 在 lithium aluminium tetrahydride 、 作用下, 以 四氢呋喃 为溶剂, 反应 1.5h, 生成 ent-帕罗醇
    参考文献:
    名称:
    [EN] ENANTIOSPECIFIC PROCESS FOR THE PREPARATION OF PAROXETINE INTERMEDIATE
    [FR] PROCEDE ENANTIOSPECIFIQUE PERMETTANT DE PREPARER UN INTERMEDIAIRE DE PAROXETINE
    摘要:
    本发明揭示了一种用于制备抗抑郁药帕罗西汀的先进中间体(-)-反式-4-(4-氟苯基)-3-羟甲基-1-甲基哌啶的改进和对映具体过程。通过使用手性酸对化合物XX进行拆分,然后对已拆分的胺进行氢化,制备了化合物XXII的方法。将化合物XXII与丙烯酸酯发生迈克尔加成反应,得到了化合物XXIII。将化合物XXIII中的羟基转化为一个脱离基,然后经过强碱处理,得到了对映具体的分子内环化哌啶衍生物XXV。将化合物XXV中的酯基还原为金属氢化物还原剂,得到了具有超过97%对映纯度的化合物I。通过在多种溶剂中进行一次结晶,将化合物I进一步纯化至>99.5%。本过程易于用于商业制备(-)-反式-4-(4-氟苯基)-3-羟甲基-1-甲基哌啶的方法。
    公开号:
    WO2005063707A1
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文献信息

  • [EN] AN IMPROVED PROCESS FOR THE PREPARATION OF PAROXETINE AND ITS INTERMEDIATE<br/>[FR] PROCÉDÉ AMÉLIORÉ DE PRÉPARATION DE PAROXÉTINE ET DE SON INTERMÉDIAIRE
    申请人:PIRAMAL ENTPR LTD
    公开号:WO2017037662A1
    公开(公告)日:2017-03-09
    The present invention provides an improved process for the preparation of N-protected ((3S,4R)- 4-(4-fluorophenyl)piperidin-3-yl)methanol (compound (A)) and further its transformation to Paroxetine and its pharmaceutically acceptable salts. The process comprises reaction of compound (II) with amido-malonate compound (C) in the presence of a chiral catalyst and optionally a dehydrating agent to obtain compound (B); followed by reduction of (B) in the presence of a reducing agent to provide compound (A).
    本发明提供了一种改进的制备N-保护基((3S,4R)-4-(4-氟苯基)哌啶-3-基)甲醇(化合物(A))的方法,并进一步将其转化为帕罗西汀及其药用可接受的盐。该方法包括在手性催化剂和可选的脱水剂的存在下,将化合物(II)与酰胺-马隆酸酯化合物(C)反应,以获得化合物(B);随后在还原剂的存在下还原(B)以提供化合物(A)。
  • Superbase-Catalyzed anti-Markovnikov Alcohol Addition Reactions to Aryl Alkenes
    作者:Chaosheng Luo、Jeffrey S. Bandar
    DOI:10.1021/jacs.8b00766
    日期:2018.3.14
    direct anti-Markovnikov addition of alcohols to aryl alkenes to access valuable β-phenethyl ethers. A diverse substrate scope of aryl alkenes and alcohols is demonstrated, including heterocyclic systems and unprotected aminoalcohols. Mechanistic studies reveal that the reaction is under equilibrium control and extensive comparisons to common inorganic bases indicate that the broad reaction scope is
    有机超强碱 P4-t-Bu 催化醇与芳基烯烃的直接反马尔科夫尼科夫加成反应,从而获得有价值的 β-苯乙醚。展示了芳基烯烃和醇的多种底物范围,包括杂环系统和未保护的氨基醇。机理研究表明,该反应处于平衡控制下,与常见无机碱的广泛比较表明,通过使用有机超强碱可以独特地实现广泛的反应范围。
  • [EN] NOVEL PROCESS FOR THE PREPARATION OF 4-ARYL-3-HYDROXYMETHYL-1-METHYLPIPERIDINES.<br/>[FR] NOUVEAU PROCEDE DE PREPARATION DE 4-ARYL-3-HYDROXYMETHYL-1-METHYLPIPERIDINES
    申请人:NATCO PHARMA LTD
    公开号:WO2004043921A1
    公开(公告)日:2004-05-27
    A novel, improved, and general process for the preparation of 4-aryl-3-hydroxymethyl-1-methylpiperidines is disclosed in the present invention. 4-(4-Fluorophenyl)-3-hydroxymethyl-1-methylpiperidine is a well-known intermediate in making the anti-depressant drug, paroxetine ((-)-trans-4-p-fluorophenyl-3-(3',4'-methylenedioxy-phenoxymethyl)piperidine). Novel N-methyl-N-[3-(4-substitutedphenyl (F, Me, OMe))-3-hydroxy]propylamines are prepared from the Mannich salts such as 3-dimethylamino- or 3-(N-methyl-N-benzylamino)-4'-substituted (F, Me, OMe) propiophenone hydrochlorides by conventional methods. The N-methyl-N-[3-(4-substitutedphenyl (H, F, Me, OMe))-3-hydroxy]propylamines thus obtained are reacted with ethyl or methyl acrylate to get the corresponding Michael addition products. The hydroxy group present in the Michael addition products is converted into a facile leaving group and treated with a strong base to get 4-aryl-N-methylpiperidine-3-carboxylates via the intramolecular cyclization in good yields. Reduction of the ester group present in these piperidine-3-carboxylates gave the title compounds as crystalline solids. Present process is easily adaptable for commercial preparation of the paroxetine intermediate (4-(4-fluorophenyl)-3-hydroxymethyl-1-methylpiperidine).
    本发明揭示了一种新颖的、改进的、通用的制备4-芳基-3-羟甲基-1-甲基哌啶的方法。4-(4-氟苯基)-3-羟甲基-1-甲基哌啶是制造抗抑郁药物帕罗西汀((-)-trans-4-p-氟苯基-3-(3',4'-亚甲二氧基苯氧甲基)哌啶)的已知中间体。新型的N-甲基-N-[3-(4-取代苯基(F,Me,OMe))-3-羟基]丙胺可通过常规方法从Mannich盐制备而来,例如3-二甲氨基或3-(N-甲基-N-苄基氨基)-4'-取代(F,Me,OMe)丙酮盐酸盐。因此获得的N-甲基-N-[3-(4-取代苯基(H,F,Me,OMe))-3-羟基]丙胺与乙基或甲基丙烯酸酯反应,得到相应的Michael加成产物。Michael加成产物中存在的羟基转化为容易离去的基团,并用强碱处理,通过分子内环化以良好的产率得到4-芳基-N-甲基哌啶-3-羧酸酯。这些哌啶-3-羧酸酯中存在的酯基还原后,得到了晶体固体的目标化合物。目前的方法易于用于商业制备帕罗西汀中间体(4-(4-氟苯基)-3-羟甲基-1-甲基哌啶)。
  • Process for preparing arylpiperidine carbinol intermediates and derivatives
    申请人:——
    公开号:US20010053862A1
    公开(公告)日:2001-12-20
    A process for the synthesis of arylpiperidine carbinol intermediates and derivatives is disclosed. A preferred process embodiment provides the synthesis of intermediate compounds of structural formula (I) and structural formula (II): 1 where X is halo, C 1 -C 10 alkoxy, C 1 -C 10 haloalkyl, or hydroxy; R 2 and R 3 are each C 1 -C 4 alkyl, and R 2 and R 3 are the same. The compound of structural formula (I) is made by condensing a corresponding cinnamonitrile with a corresponding diester malonate. The compound of structural formula (II) in the (±)-trans configuration is obtained by hydrogenating the compound of structural formula (I). The compounds of structural formula (I) and structural formula (II) are useful chemical intermediates for synthesizing 4-arylpiperidine-3-carbinols and their derivatives in (−)-trans configuration.
    本发明揭示了一种合成芳基哌啶羧醇中间体和衍生物的方法。首选的方法实施方式提供了结构式(I)和结构式(II)的中间化合物的合成:其中X是卤素,C1-C10烷氧基,C1-C10卤代烷基或羟基;R2和R3均为C1-C4烷基,并且R2和R3相同。结构式(I)的化合物是通过将相应的肉桂腈与相应的二酯丙二酸酯缩合而制得的。在(±)-反式构型下,通过氢化结构式(I)的化合物可获得结构式(II)的化合物。结构式(I)和结构式(II)的化合物是合成(-)-反式构型的4-芳基哌啶-3-羧醇及其衍生物的有用化学中间体。
  • Novel process
    申请人:SmithKline Beecham p.l.c.
    公开号:US20020010155A1
    公开(公告)日:2002-01-24
    A process for the preparation of a 4-aryl-3-oxymethyl-piperidine of structure (1) 1 in which R is hydrogen or an alkyl, arylalkyl, allyl, acyl, carbonyloxyalkyl, carbonyloxyaryl, or carbonyloxyalkylaryl group, and Y is a hydrogen atom or an optionally substituted alkyl, arylalkyl, or aryl group, from a carboxy derivative of structure (2) 2 where A is oxygen or sulphar, X is one or more of hydrogen, or a readily reducible group, Z represents either a hydrogen atom or an OY′ group in which Y′ is independently selected from the same groups as Y, and the broken line circle indicates bonding, appropriate to a tetrahydropyridine, dihydropyridine, pyridine, or piperidine ring said process comprising (a) when Y is a hydrogen atom, reducing the compound of structure (2), or (b) when Y is other than a hydrogen atom (i) forming an ether from the alcohol product of step (a), (ii) etherifying the aldehyde compound of structure (2) in which Z is hydrogen, or (iii) reducing the ester compound of structure (2) in which Z is OY′.
    一种制备结构(1)中的4-芳基-3-氧甲基-哌啶的方法,其中R是氢或烷基、芳基烷基、烯丙基、酰基、羰基氧烷基、羰基氧芳基或羰基氧烷基芳基,Y是氢原子或可选择取代的烷基、芳基烷基或芳基,从结构(2)中的羧衍生物进行,其中A是氧或硫,X是一个或多个氢或易还原基团,Z代表氢原子或OY′基团,其中Y′独立选择自Y相同的基团,中断线圆表示键合,适用于四氢吡啶、二氢吡啶、吡啶或哌啶环的过程包括(a)当Y是氢原子时,还原结构(2)的化合物,或(b)当Y不是氢原子时(i)从步骤(a)的醇产物中形成醚,(ii)使结构(2)中Z为氢的醛化合物醚化,或(iii)还原结构(2)中Z为OY′的酯化合物。
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