((4S,6R)-6-(2-tert-butoxy-2-oxoethyl)-2,2-dimethyl-1,3-dioxan-4-yl)methyl benzoate | 131666-50-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ((4S,6R)-6-(2-tert-butoxy-2-oxoethyl)-2,2-dimethyl-1,3-dioxan-4-yl)methyl benzoate
• 英文别名: (4R-cis)-6-[(benzoyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid, 1,1-dimethylethyl ester；(4R-cis)-6-[(benzoyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetic acid,1,1-dimethylethyl ester；2-[(4R,6S)-2,2-dimethyl-6-benzoyloxymethyl-1,3-dioxan-4-yl]acetic tert-butyl ester；tert.-butyl (3R,5S)-6-benzoyloxy-3,5-O-isopropylidene-3,5-dihydroxyhexanoate；2-[(4R, 6S)-2,2-dimethyl-6-benzoyloxymethyl-1,3-dioxan-4-yl]acetic tert-butyl ester；[(4S,6R)-2,2-dimethyl-6-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-1,3-dioxan-4-yl]methyl benzoate
• CAS: 131666-50-7
• 化学式: C₂₀H₂₈O₆
• 分子量: 364.439
• InChiKey: KHHRHONIHYEAHX-CVEARBPZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  71.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ((4S,6R)-6-(2-tert-butoxy-2-oxoethyl)-2,2-dimethyl-1,3-dioxan-4-yl)methyl benzoate 在 sodium hypochlorite 、 2,2,6,6-四甲基哌啶氧化物 、 4-甲基苯磺酸吡啶 、 碳酸氢钠 、 potassium carbonate 、 溶剂黄146 、 potassium bromide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 16.0h， 生成 tert-butyl-2((4R,6S)-6-{(E)-2-[4-(4-Fluorophenyl)-6-isopropyl-2-(N-methylmethylsulfon-amido)-pyrimidin-5-yl]-vinyl}-2-phenyl-[1,3]dioxan-4-yl)acetate
  参考文献：
  名称：

  스타틴의 중간체, 이의 제조방법 및 이를 이용한 로수바스타틴의 제조방법

  摘要：

  本发明提供了一种制备洛索巴斯汀的关键中间体（化学式IV）的新型制备方法，以及用于该制备方法的新型中间体和利用该中间体制备洛索巴斯汀盐酸盐的方法。本发明的新型中间体可以在温和条件下高纯度和高产率地制备，从而可以简单、高效地大规模生产洛索巴斯汀的中间体和洛索巴斯汀盐酸盐，而无需复杂的工艺。

  公开号：

  KR20160126700A
• 作为产物：
  描述：

  (4R-Cis)-6-羟甲基-2,2-二甲基-1,3-二氧六环-4-乙酸叔丁酯 、 苯甲酰氯 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 以88%的产率得到((4S,6R)-6-(2-tert-butoxy-2-oxoethyl)-2,2-dimethyl-1,3-dioxan-4-yl)methyl benzoate
  参考文献：
  名称：

  스타틴의 중간체, 이의 제조방법 및 이를 이용한 로수바스타틴의 제조방법

  摘要：

  本发明提供了一种制备洛索巴斯汀的关键中间体（化学式IV）的新型制备方法，以及用于该制备方法的新型中间体和利用该中间体制备洛索巴斯汀盐酸盐的方法。本发明的新型中间体可以在温和条件下高纯度和高产率地制备，从而可以简单、高效地大规模生产洛索巴斯汀的中间体和洛索巴斯汀盐酸盐，而无需复杂的工艺。

  公开号：

  KR20160126700A

文献信息

• Process for the production of 3,5,6-trihydroxyhexanoic acid derivative
  申请人：Kanegafuchi Chemical Industry Co., Ltd.

  公开号：US04983759A1

  公开（公告）日：1991-01-08

  A compound of a 3,5,6-trihydroxyhexanoic acid derivative of the formula: ##STR1## wherein P.sup.1 and P.sup.2 are independently hydrogen atoms or hydroxy-protecting groups, or together form a ring, and R is an alkyl group is effectively prepared by a process comprising steps of: reacting a butyronitrile derivative of the formula: ##STR2## wherein P.sup.1 and P.sup.2 are the same as defined above with an .alpha.-haloacetate of the formula: X--CH.sub.2 --COOR (III) wherein X is a halogen atom, and R is the same as defined above in the presence of a metallic catalyst selected from the group consisting zinc and zinc-copper to form a keto acid derivative of the formula: ##STR3## wherein P.sup.1, P.sup.2 and R are the same as defined above, and then reducing the obtained keto-acid derivative of the formula (IV).

  一种化合物，其为3,5,6-三羟基己酸衍生物，化学式如下：##STR1## 其中P1和P2分别是氢原子或羟基保护基，或者一起形成一个环，R为烷基基团，通过以下步骤有效制备：将以下化学式的丁腈衍生物：##STR2## 其中P1和P2的定义与上述相同，与以下化学式的α-卤代乙酸酯：X--CH2--COOR (III) 反应，其中X为卤素原子，R的定义与上述相同，在选择自锌和锌-铜组成的金属催化剂存在下，形成以下酮酸衍生物：##STR3## 其中P1、P2和R的定义与上述相同，然后还原得到的酮酸衍生物（IV）。
• Application of chiral 2-isoxazoline for the synthesis of <i>syn</i>-1,3-diol analogs
  作者：Juanjuan Feng、Tianyu Li、Jiaxin Zhang、Peng Jiao

  DOI：10.3762/bjoc.15.179

  日期：——

  The asymmetric cycloaddition of TIPS nitronate catalyzed by “Cu(II)-bisoxazoline” gave the 2-isoxazoline product in 95% yield, which was converted into tert-butyl (3S,5R)-6-hydroxy-3,5-O-isopropylidene-3,5-dihydroxyhexanoate in 14 steps through a β-hydroxy ketone.

  TIPS硝酸酯的不对称环加成反应在“Cu(II)-双噁唑啉”催化下，产率为95%得到2-异噁唑醇产物，经过14步转化成（3S,5R）-6-羟基-3,5-O-异丙基-3,5-二羟基己酸叔丁酯，中间通过β-羟基酮。
• Process for preparing optically active 2-[6-(hydroxy-methyl)-1,3-dioxan-4-yl] acetic acid derivatives
  申请人：Nishiyama Akira

  公开号：US20050080277A1

  公开（公告）日：2005-04-14

  The present invention is to provide a production technology by which an optically active 2-[6-(hydroxymethyl)-1,3-dioxan-4-yl]acetic acid derivative, which are of value as pharmaceutical intermediates, can be produced from inexpensive and readily available starting materials without using any extraordinary equipment such as an ultra-low-temperature reactor. The present invention is a production process of an optically active 2-[6-(hydroxymethyl)-1,3-dioxan-4-yl]acetic acid derivative which comprises reacting an enolate, prepared by permitting a base or a 0-valent metal to act on an acetic acid ester derivative with (S)-β-hydroxy-γ-butyrolactone at a temperature not lower than −30° C. to give a dihydroxyoxohexanoic acid derivative, treating the same with an acylating agent in the presence of a base to produce a dihydroxyoxohexanoic acid monoacyl derivative, reducing this compound with a microorganism to produce a trihydroxyhexanoic acid monoacyl derivative, treating this compound with an acetal-forming reagent in the presence of an acid catalyst to produce an acyloxymethyldioxanylacetic acid derivative, and finally, subjecting this compound to solvolysis in the presence of a base.

  本发明旨在提供一种生产技术，通过该技术可以从廉价且易得的起始材料中生产出具有药物中间体价值的光学活性2-[6-(羟甲基)-1,3-二氧杂环戊-4-基]乙酸衍生物，而无需使用任何特殊设备，如超低温反应器。本发明是一种光学活性2-[6-(羟甲基)-1,3-二氧杂环戊-4-基]乙酸衍生物的生产过程，包括将碱或0价金属作用于乙酸酯衍生物制备出的烯醇，与(S)-β-羟基-γ-丁内酯在不低于-30℃的温度下反应，得到二羟基氧代己酸衍生物，用酰化剂在碱的存在下处理，以产生二羟基氧代己酸单酰衍生物，用微生物还原该化合物以产生三羟基己酸单酰衍生物，用酸催化剂存在下的缩醛试剂处理该化合物，以产生酰氧甲基二氧杂环己酸衍生物，最后，在碱的存在下进行溶剂解离。
• Process for the preparation of 1,3-dioxane derivatives useful in the
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US05594153A1

  公开（公告）日：1997-01-14

  A novel, overall process for the preparation of a compound of the formula I: ##STR1## where R.sup.1 and R.sup.2 are each independently hydrogen, an alkyl group, a cycloalkyl group, an aryl group or, taken together with the carbon atom to which they are attached, form a cycloalkyl group; and R.sup.3 is hydrogen, an alkyl group, or an aryl group, or salts thereof, useful as intermediates in the preparation of HMG-CoA reductase inhibitors; novel methods within the overall process; and novel intermediates produced by those methods.

  一种用于制备公式I化合物的新型全过程：##STR1## 其中，R.sup.1和R.sup.2分别独立地表示氢、烷基、环烷基、芳基或与它们连接的碳原子形成环烷基；R.sup.3表示氢、烷基或芳基，或其盐，可用作制备HMG-CoA还原酶抑制剂的中间体；该全过程中的新型方法；以及由这些方法产生的新型中间体。
• PROCESS FOR PREPARING OPTICALLY ACTIVE 2- 6-(HYDROXY-METHYL)-1,3-DIOXAN-4-YL]ACETIC ACID DERIVATIVES
  申请人：KANEKA CORPORATION

  公开号：EP1288213A1

  公开（公告）日：2003-03-05

  The present invention is to provide a production technology by which an optically active 2-[6-(hydroxymethyl)-1,3-dioxan-4-yl]acetic acid derivative, which are of value as pharmaceutical intermediates, can be produced from inexpensive and readily available starting materials without using any extraordinary equipment such as an ultra-low-temperature reactor. The present invention is a production process of an optically active 2-[6-(hydroxymethyl)-1,3-dioxan-4-yl]acetic acid derivative    which comprises reacting an enolate, prepared by permitting a base or a 0-valent metal to act on an acetic acid ester derivative with (S)-β-hydroxy-γ-butyrolactone at a temperature not lower than -30°C to give a dihydroxyoxohexanoic acid derivative,    treating the same with an acylating agent in the presence of a base to produce a dihydroxyoxohexanoic acid monoacyl derivative,    reducing this compound with a microorganism to produce a trihydroxyhexanoic acid monoacyl derivative,    treating this compound with an acetal-forming reagent in the presence of an acid catalyst to produce an acyloxymethyldioxanylacetic acid derivative, and    finally, subjecting this compound to solvolysis in the presence of a base.

  本发明旨在提供一种生产技术，通过该技术，无需使用超低温反应器等任何特殊设备，即可从廉价易得的起始材料中生产出具有光学活性的 2-[6-(羟甲基)-1,3-二氧杂环戊烷-4-基]乙酸衍生物，该衍生物具有医药中间体的价值。 本发明是一种具有光学活性的 2-[6-(羟甲基)-1,3-二氧杂环戊烷-4-基]乙酸衍生物的生产工艺。 其中包括在不低于-30℃的温度下，将通过允许碱或 0 价金属作用于乙酸酯衍生物而制备的烯醇与(S)-β-羟基-γ-丁内酯反应，得到二羟基氧代己酸衍生物、 在碱存在下，用酰化剂处理该衍生物，生成二羟基氧代己酸单酰基衍生物、 用微生物还原该化合物，生成三羟基己酸单乙酰衍生物、 在酸催化剂存在下，用乙缩醛形成试剂处理该化合物，生成酰氧基甲基二氧杂环乙酸衍生物，以及 最后，使该化合物在碱存在下发生溶解反应。