(2S)-2-methoxy-2-methyl-pent-1-ol | 471257-44-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2S)-2-methoxy-2-methyl-pent-1-ol
• 英文别名: (2S)-2-methoxy-2-methyl-1-pentanol；(2S)-2-methoxy-2-methylpentan-1-ol
• CAS: 471257-44-0
• 化学式: C₇H₁₆O₂
• 分子量: 132.203
• InChiKey: MBMZPJJQINFTTI-ZETCQYMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  9
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (2S)-2-methoxy-2-methyl-pent-1-ol 在 三甲基氯硅烷 、 copper(I) bromide dimethylsulfide complex 、 pyridine-SO3 complex 、 三氟甲磺酸 、 4-甲基苯磺酸吡啶 、 三乙基硼氢化锂 、 sodium sulfate 、 三乙胺 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 反应 16.42h， 生成 tert-butyl (2R,3S)-5-hydroxy-2-((1R,2S)-2-methoxy-2-methyl-1-((tritylthio)amino)pentyl)-3-((Z)-prop-1-en-1-yl)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  在合成流感神经氨酸酶抑制剂中，高度非对映选择性的乙烯基曼尼希缩合和（Z）-丙烯基铜酸盐的1,4-共轭加成

  摘要：

  已经开发了神经氨酸酶流感抑制剂A-322278的实用合成方法。通过酶介导的酯水解将不对称性引入合成中。N -Boc-2-叔丁基二甲基甲硅烷基氧基吡咯（TBSOP）和N-（三苯基甲基亚磺酰基）亚胺的高度非对映选择性乙烯基类曼尼希缩合反应在热力学控制下进行以组装骨架。观察到在添加1，4-共轭物期间从铜酸盐试剂转移（Z）-和（E）-丙烯基部分的明显的温度依赖性速率差异。将氰化物非常有选择性地加到N-酰基亚胺中间体上来控制最终的立体中心。

  DOI：

  10.1016/s0957-4166(03)00597-4
• 作为产物：
  描述：

  (2E)-2-methyl-2-penten-1-ol 在 4 A molecular sieve titanium(IV) isopropylate 、 叔丁基过氧化氢 、 lithium aluminium tetrahydride 、 D-(-)-酒石酸二甲酯 、 氢气 、 sodium hexamethyldisilazane 、 sodium hydride 、 三乙胺 、 三甲氧基磷 作用下， 以 四氢呋喃 、 癸烷 、 二氯甲烷 为溶剂， 反应 41.0h， 生成 (2S)-2-methoxy-2-methyl-pent-1-ol
  参考文献：
  名称：

  Enantioselective Synthesis of Antiinfluenza Compound A-315675

  摘要：

  Drug discovery efforts at Abbott Laboratories have led to the identification of influenza neuraminidase inhibitor A-315675 (1) as a candidate for development as an antiinfluenza drug. A convergent, stereoselective synthesis of this highly functionalized pyrrolidine is reported that utilizes pyrrolinone 2 as the key intermediate. The C5, C6 stereochemistry was established through a diastereoselective condensation of chiral imine compound 3 with silyloxypyrrole 4 to give pyrrolinone 2. The stereochemical outcome of this reaction depended critically on the choice of the imine functional group (FG), with tritylsulfenyl and (R)-toluenesulfinyl providing the desired products in good yields as crystalline intermediates. Conversion of pyrrolinone 2 into 1 was accomplished in seven subsequent steps, including Michael addition of cis-1-propenylcuprate at C4 and introduction of a cyano group as a carboxylic acid equivalent at C2.

  DOI：

  10.1021/jo0162890

文献信息

• Process for the preparation of substituted pyrrolidine neuraminidase inhibitors
  申请人：——

  公开号：US20030055297A1

  公开（公告）日：2003-03-20

  A process for the preparation of neuraminidase inhibitors having structural formula (28) 1 or therapeutically acceptable salts thereof, in which R 1 is alkyl, cycloalkyl, cycloalkylalkyl, or arylalkyl; R 2 is alkyl, cycloalkyl, cycloalkylalkyl, or arylalkyl; R 4 is alkyl, cycloalkyalkyl, or aryl-(C 2 -C 4 -alkyl); R 10 is methyl, ethyl, iso-propyl, or vinyl; and R 12 is hydrogen or alkyl and intermediates useful for the process are disclosed.

  一种用于制备具有结构式（28）1或其治疗上可接受的盐的神经氨酸酶抑制剂的方法，其中R1是烷基，环烷基，环烷基烷基或芳基烷基；R2是烷基，环烷基，环烷基烷基或芳基烷基；R4是烷基，环烷烷基或芳基（C2-C4-烷基）；R10是甲基，乙基，异丙基或乙烯基；和R12是氢或烷基，公开了用于该方法的中间体。
• [EN] PROCESS FOR THE PREPARATION OF SUBSTITUTED PYRROLIDINE NEURAMINIDASE INHIBITORS<br/>[FR] PROCEDE DE PREPARATION D'INHIBITEURS DE PYRROLIDINE NEURAMINIDASE SUBSTITUE
  申请人：ABBOTT LAB

  公开号：WO2002081441A1

  公开（公告）日：2002-10-17

  A process for the preparation of neuraminidase inhibitors having structural formula (28) or therapeutically acceptable salts thereof, in which R1 is alkyl, cycloalkyl, cycloalkylalkyl, or arylalkyl; R2 is alkyl, cycloalkyl, cycloalkylalkyl, or arylalkyl; R4 is alkyl, cycloalkyalkyl, or aryl-(C2-C4-alkyl); R10 is methyl, ethyl, iso-propyl, or vinyl; and R12 is hydrogen or alkyl and intermediates useful for the process are disclosed.
• Enantioselective Synthesis of Antiinfluenza Compound A-315675
  作者：David A. DeGoey、Hui-Ju Chen、William J. Flosi、David J. Grampovnik、Clinton M. Yeung、Larry L. Klein、Dale J. Kempf

  DOI：10.1021/jo0162890

  日期：2002.8.1

  Drug discovery efforts at Abbott Laboratories have led to the identification of influenza neuraminidase inhibitor A-315675 (1) as a candidate for development as an antiinfluenza drug. A convergent, stereoselective synthesis of this highly functionalized pyrrolidine is reported that utilizes pyrrolinone 2 as the key intermediate. The C5, C6 stereochemistry was established through a diastereoselective condensation of chiral imine compound 3 with silyloxypyrrole 4 to give pyrrolinone 2. The stereochemical outcome of this reaction depended critically on the choice of the imine functional group (FG), with tritylsulfenyl and (R)-toluenesulfinyl providing the desired products in good yields as crystalline intermediates. Conversion of pyrrolinone 2 into 1 was accomplished in seven subsequent steps, including Michael addition of cis-1-propenylcuprate at C4 and introduction of a cyano group as a carboxylic acid equivalent at C2.
• A highly diastereoselective vinylogous Mannich condensation and 1,4-conjugate addition of (Z)-propenyl cuprate in the synthesis of an influenza neuraminidase inhibitor
  作者：David M. Barnes、Lakshmi Bhagavatula、John DeMattei、Ashok Gupta、David R. Hill、Sukumar Manna、Maureen A. McLaughlin、Paul Nichols、Ramiya Premchandran、Michael W. Rasmussen、Zhenping Tian、Steven J. Wittenberger

  DOI：10.1016/s0957-4166(03)00597-4

  日期：2003.11

  A practical synthesis of neuraminidase influenza inhibitor, A-322278, has been developed. Asymmetry is introduced into the synthesis by an enzyme mediated ester hydrolysis. A highly diastereoselective vinylogous Mannich condensation reaction of N-Boc-2-tert-butyldimethylsilyloxypyrrole (TBSOP) and an N-(triphenylmethylsulfenyl)imine proceeds under thermodynamic control to assemble the framework. A

  已经开发了神经氨酸酶流感抑制剂A-322278的实用合成方法。通过酶介导的酯水解将不对称性引入合成中。N -Boc-2-叔丁基二甲基甲硅烷基氧基吡咯（TBSOP）和N-（三苯基甲基亚磺酰基）亚胺的高度非对映选择性乙烯基类曼尼希缩合反应在热力学控制下进行以组装骨架。观察到在添加1，4-共轭物期间从铜酸盐试剂转移（Z）-和（E）-丙烯基部分的明显的温度依赖性速率差异。将氰化物非常有选择性地加到N-酰基亚胺中间体上来控制最终的立体中心。