7-benzoyloxy-4-bromomethyl-3-[(2,4-dibenzoyloxy)-phenyl]coumarin | 554433-12-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 缩酚酸和缩酚酸环醚类
• 英文名称: 7-benzoyloxy-4-bromomethyl-3-[(2,4-dibenzoyloxy)-phenyl]coumarin
• 英文别名: 4-[7-(Benzoyloxy)-4-(bromomethyl)-2-oxo-2H-1-benzopyran-3-yl]-1,3-phenylene dibenzoate；[4-(bromomethyl)-3-(2,4-dibenzoyloxyphenyl)-2-oxochromen-7-yl] benzoate
• CAS: 554433-12-4
• 化学式: C₃₇H₂₃BrO₈
• 分子量: 675.489
• InChiKey: KVATVEMZXLYFBO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.9
• 重原子数：
  46
• 可旋转键数：
  11
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.03
• 拓扑面积：
  105
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2,4-二羟基苯乙酮 在 溴 、 吡啶盐酸盐 、 三乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 7-benzoyloxy-4-bromomethyl-3-[(2,4-dibenzoyloxy)-phenyl]coumarin
  参考文献：
  名称：

  四环杂化合物的合成作为选择性雌激素受体调节剂。第1部分。放大开发2,5,8取代的5,11-二氢色酚[4,3- c ]苯二甲基衍生物的工艺开发

  摘要：

  不对称的苯并吡喃并苯并吡喃化合物是新型的选择性雌激素受体调节剂（SERM）。开发了一种可重现的非色谱方法，以制备数百克数量的5-（4-（2-（2-哌啶-1-基）乙氧基）苯基）-5,11-二氢苯并[4,3 - c ]苯二甲基-2,8 -二基-双（2，2-二甲基丙酸酯）（14）。经过三个扩大规模的推广活动后，该11步合成的总产率从0.17％提高到7.1％。

  DOI：

  10.1021/op700020f

文献信息

• Development of a Scalable Synthetic Process for Selective Bromination of 4-Methyl-3,7-Substituted Coumarins
  作者：Xun Li、Nareshkumar Jain、Ronald K. Russell、Robert Ma、Shawn Branum、Jiayi Xu、Zhihua Sui

  DOI：10.1021/op050242p

  日期：2006.3.1

  The hydroxyl-protected coumarin derivatives 6a-e of 4-methyl3-(2,4-dihydroxyphenyl)-7-hydroxycoumarin (4) are key intermediates in the synthesis of unsymmetrical benzopyranobenzopyran compounds, a novel series of selective estrogen receptor modulators (SERMs). Free radical bromination of the 4-methyl group on 7-acetoxy-3-[(2,4-diacetoxy)phenyl]-4-methylcoumarin (6a) with NBS resulted in incomplete reactions and low to moderate yields (25-44%) of 4-bromomethyl product 7a. Lithiation of the 4-methyl group of coumarins 6b (R = SEM), 6c (R = MOM) and 6d (R = Bz) with LDA (1.1 - 1.7 equiv) or LHMDS (1.2-1.7 equiv) generated carbanion in THF at -76 degrees C, which was quenched with bromine (1.5-2.0 equiv) to afford 4-bromomethyl derivatives 7b-d in good yields (80-90%) in small scale reactions (2-20 g). The reaction yields declined to similar to 70% when the scale was increased to >= 80 g. Furthermore, treatment of 3-[(2,4-dimethoxy)phenyl]-7-methoxy-4-methylcoumarin (6e) with LHMDS (1.08 equiv) in THF followed by rapid inverse quenched with NBS (1.10 equiv) in THF at -76 degrees C, selectively produced the desired 4-bromomethyl compound 7e in excellent yield (> 90%) in both small (2-8 g) and large (80-150 g) scale reactions. A non-chromatographic process was developed to prepare 6e. This selective and efficient procedure was successfully transferred to the pilot plant to produce multikilograms of 4-bromomethyl coumarin 7e.
• US7329654B2
  申请人：——

  公开号：US7329654B2

  公开（公告）日：2008-02-12
• Synthesis of Tetracyclic Heterocompounds as Selective Estrogen Receptor Modulators. Part 1. Process Development for Scale-up of 2,5,8-Substituted 5,11-Dihydrochromeno[4,3-<i>c</i>]chromene Derivatives
  作者：Xun Li、Michael Reuman、Ronald K. Russell、Richard Adams、Robert Ma、Sandra Beish,、Shawn Branum、Scott Youells、Jerry Roberts、Nareshkumar Jain、Ramesh Kanojia、Zhihua Sui

  DOI：10.1021/op700020f

  日期：2007.5.1

  compounds are novel selective estrogen receptor modulators (SERMs). A reproducible and nonchromatographic process was developed to prepare multihundred gram quantities of 5-(4-(2-(piperidin-1-yl)ethoxy)phenyl)-5,11-dihydrochromeno[4,3-c]chromene-2,8-diyl-bis(2,2-dimethylpropanoate) (14). The overall yield of this 11-step synthesis was improved from 0.17% to 7.1% after three scale-up campaigns.

  不对称的苯并吡喃并苯并吡喃化合物是新型的选择性雌激素受体调节剂（SERM）。开发了一种可重现的非色谱方法，以制备数百克数量的5-（4-（2-（2-哌啶-1-基）乙氧基）苯基）-5,11-二氢苯并[4,3 - c ]苯二甲基-2,8 -二基-双（2，2-二甲基丙酸酯）（14）。经过三个扩大规模的推广活动后，该11步合成的总产率从0.17％提高到7.1％。