(4S,6S)-6-(chloromethyl)-4-hydroxyoxan-2-one | 135999-59-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: (4S,6S)-6-(chloromethyl)-4-hydroxyoxan-2-one
• CAS: 135999-59-6
• 化学式: C₆H₉ClO₃
• 分子量: 164.589
• InChiKey: KLWVUDQIPZIXER-WHFBIAKZSA-N

物化性质

• 沸点：
  342.2±27.0 °C(Predicted)
• 密度：
  1.333±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4S,6S)-6-(chloromethyl)-4-hydroxyoxan-2-one 在 对甲苯磺酸 作用下， 以 甲醇 、 苯 为溶剂， 反应 1.5h， 生成 (3R,5S)-5,6-epoxy-3-hydroxyhexanoate
  参考文献：
  名称：

  Lipase-catalyzed asymmetric synthesis of 6-(3-chloro-2-hydroxypropyl)-1,3-dioxin-4-ones and their conversion to chiral 5,6-epoxyhexanoates

  摘要：

  Highly enantioselective syntheses of (R)- and (S)-6-(3-chloro-2-hydroxypropyl)-1,3-dioxin-4-ones by means of lipase-catalyzed kinetic resolutions are described. Chiral dioxinones thus obtained have been converted to optically active 5,6-epoxyhexanoates, which are important precursors for a series of biologically active compounds.

  DOI：

  10.1016/s0957-4166(00)82114-x
• 作为产物：
  描述：

  6-[(2S)-3-chloro-2-hydroxypropyl]-2,2-dimethyl-1,3-dioxin-4-one 在 platinum(IV) oxide 氢气 、 potassium carbonate 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 7.0h， 生成 (4S,6S)-6-(chloromethyl)-4-hydroxyoxan-2-one
  参考文献：
  名称：

  Lipase-catalyzed asymmetric synthesis of 6-(3-chloro-2-hydroxypropyl)-1,3-dioxin-4-ones and their conversion to chiral 5,6-epoxyhexanoates

  摘要：

  Highly enantioselective syntheses of (R)- and (S)-6-(3-chloro-2-hydroxypropyl)-1,3-dioxin-4-ones by means of lipase-catalyzed kinetic resolutions are described. Chiral dioxinones thus obtained have been converted to optically active 5,6-epoxyhexanoates, which are important precursors for a series of biologically active compounds.

  DOI：

  10.1016/s0957-4166(00)82114-x

文献信息

• Synthetic studies on statins. Part 3: A facile synthesis of rosuvastatin calcium through catalytic enantioselective allylation strategy
  作者：Xiaofei Chen、Fangjun Xiong、Chen Zheng、Jie Li、Fener Chen

  DOI：10.1016/j.tet.2014.06.077

  日期：2014.9

  A concise and stereocontrolled synthesis of rosuvastatin calcium has been accomplished, with the key steps including a Keck enantioselective allylation of chloroacetaldehyde with allyltributylstannane to install 5R-stereocenter and a VO(acac)2-catalyzed syn-diastereoselective epoxidation of (S)-1-chloropent-4-en-2-ol to set the requisite 3R-chirality.

  罗苏伐他汀钙的简明和立体控制合成已经完成，关键步骤包括氯乙醛与烯丙基三丁基锡烷的Keck对映选择性烯丙基化以安装5 R-立体中心和VO（acac）2-催化的（S）-1的顺-非对映选择性环氧化-chloropent-4-en-2-ol设置必要的3 R手性。
• [EN] PROCESS FOR THE PREPARATION OF 2-(6-SUBSTITUTED-1,3-DIOXANE-4-YL)ACETIC ACID DERIVATIVES<br/>[FR] PROCEDE DE PREPARATION DE DERIVES D'ACIDE 2-(1,3-DIOXANE-4-YL SUBSTITUE EN 6)ACETIQUE
  申请人：DSM NV

  公开号：WO2002006266A1

  公开（公告）日：2002-01-24

  The invention relates to the preparation of 2-(6-substituted-1,3-dioxane-4-yl)acetic acid derivatives of formula (1), where X stands for a leaving group, and R1, R2, and R3 each independently stand for an alkyl group with 1-3 carbon atoms from 4-hydroxy-6-X-substituted-methyl-tetrahydropyran-2-one compounds, where X is as defined above, with the aid of an acetalization agent, in the presence of an acid catalyst. The invention also relates to the novel compounds of formula (1) as well as salts and acids to be prepared from these, with the OR3 group in formula (1) being replaced by an OY group, where X, R1 and R2 have the meanings defined above and where Y stands for an alkaline (earth) metal or a substituted or unsubstituted ammonium group or stands for hydrogen, and to the novel compounds of formula (2). The products concerned are, after conversion into the t-butyl ester of 2-(6-hydroxymethyl-1,3-dioxane-4-yl)acetic acid, important as intermediary products in the preparation of statins.

  本发明涉及从4-羟基-6-X-取代甲基四氢吡喃-2-酮化合物（其中X代表离去基，R1、R2和R3分别独立地代表具有1-3个碳原子的烷基基团）中，在醛缩剂的帮助下，在酸催化剂的存在下制备公式（1）的2-（6-取代-1,3-二氧杂环-4-基）乙酸衍生物，所述公式（1）中OR3基团被OY基团取代，其中X、R1和R2具有上述定义，Y代表碱金属或取代或未取代的铵基团或代表氢，以及公式（2）的新化合物，本发明还涉及从这些化合物制备的盐和酸。所述产物在转化为2-（6-羟甲基-1,3-二氧杂环-4-基）乙酸叔丁酯后，作为合成他汀类药物的中间体物质具有重要作用。
• PROCESS FOR THE PREPARATION OF ENANTIOMERICALLY PURE 4-HYDROXYTETRAHYDRO-2-PYRANONE DERIVATIVES
  申请人：ZENECA LIMITED

  公开号：EP0604483A1

  公开（公告）日：1994-07-06
• PROCESS FOR THE PREPARATION OF 2-(6-SUBSTITUTED-1,3-DIOXANE-4-YL)ACETIC ACID DERIVATIVES
  申请人：DSM N.V.

  公开号：EP1317440A1

  公开（公告）日：2003-06-11
• ENZYMATIC SYNTHESIS OF ACTIVE PHARMACEUTICAL INGREDIENT AND INTERMEDIATES THEREOF
  申请人：LEK Pharmaceuticals d.d.

  公开号：EP2655650A2

  公开（公告）日：2013-10-30