(R)-4-fluoromethyldihydro-3H-furan-2-one | 916069-81-3

• 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: (R)-4-fluoromethyldihydro-3H-furan-2-one
• 英文别名: (R)-3-fluoromethyl-γ-butyrolactone；(R)-4-fluoromethyl-dihydro-furan-2-one；(R)-4-(Fluoromethyl)dihydrofuran-2(3H)-one；(4R)-4-(fluoromethyl)oxolan-2-one
• CAS: 916069-81-3
• 化学式: C₅H₇FO₂
• 分子量: 118.108
• InChiKey: SNOBQHSFTVYKRO-BYPYZUCNSA-N

物化性质

• 沸点：
  233.2±5.0 °C(Predicted)
• 密度：
  1.149±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  8
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-4-fluoromethyldihydro-3H-furan-2-one 在 氯化亚砜 、 zinc(II) chloride 作用下， 反应 72.0h， 生成 (3S)-3-(chloromethyl)-4-fluorobutanoyl chloride
  参考文献：
  名称：

  卡格列汀的发现：一种有效且长效的二肽基肽酶IV抑制剂，可用于治疗2型糖尿病

  摘要：

  针对一类基于S1特异性口袋中具有非芳族取代基的氨基苯并[ a ]喹唑啉的DPP-IV抑制剂的设计，合成和SAR进行了描述。选择其代表卡格列汀（8p）进行临床开发。还介绍了其与酶复合的X射线结构以及2型糖尿病动物模型中的早期功效数据。

  DOI：

  10.1016/j.bmcl.2009.12.024
• 作为产物：
  描述：

  4-hydroxymethyl-5H-furan-2-one 在 [Ru(OAc)2((R)-3,5-i-Pr-4-MeOBIPHEP)] 、 氢气 、 [双(2-甲氧基乙基)胺]三氟化硫 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 2.83h， 生成 (R)-4-fluoromethyldihydro-3H-furan-2-one
  参考文献：
  名称：

  Development of a Scalable Synthesis of (S)-3-Fluoromethyl-γ-butyrolactone, Building Block for Carmegliptin’s Lactam Moiety

  摘要：

  Several new routes are reported for the synthesis of (S)-3-fluoromethyl-gamma-butyrolactone. An asymmetric hydrogenation-based synthesis was chosen as the enabling route to produce the lactone on a 10-kg scale. A superior stereoselective route starting from (S)-tert-butyl glycidyl ether which afforded the desired lactone in three steps with similar to 50% overall yield was finally selected for further development and production.

  DOI：

  10.1021/op200019k

文献信息

• Process for the preparation of (S)-4-fluoromethyl-dihydro-furan-2-one useful in the preparation of the DPP-IV inhibitor (S)-1 ((2S,3S,11bS)-2-amino-9,10-dimethoxy-1,3,4,6,7, 11b-hexahydro-2h-pyrido[2,1-a] isoquinolin-3-yl)-4-fluoromethyl-pyrrolidin-2-one
  申请人：Abrecht Stefan

  公开号：US20060270853A1

  公开（公告）日：2006-11-30

  This invention relates to a process of the preparation of the novel intermediate (S)-4-fluoromethyl-dihydro-furan-2-one of the formula and with its use for the manufacture of pyrido[2,1-a]isoquinoline derivatives of the formula which are useful for the treatment and/or prophylaxis of diseases which are associated with DPP IV.

  本发明涉及制备新中间体(S)-4-氟甲基-二氢呋喃-2-酮的方法，其化学式为：并利用该中间体制备式为：的吡啶[2,1-a]异喹啉衍生物，这些衍生物对于治疗和/或预防与DPP IV相关的疾病是有用的。
• Discovery of carmegliptin: A potent and long-acting dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes
  作者：Patrizio Mattei、Markus Boehringer、Patrick Di Giorgio、Holger Fischer、Michael Hennig、Joerg Huwyler、Buelent Koçer、Bernd Kuhn、Bernd M. Loeffler、Alexander MacDonald、Robert Narquizian、Etienne Rauber、Elena Sebokova、Urs Sprecher

  DOI：10.1016/j.bmcl.2009.12.024

  日期：2010.2

  synthesis, and SAR are described for a class of DPP-IV inhibitors based on aminobenzo[a]quinolizines with non-aromatic substituents in the S1 specificity pocket. One representative thereof, carmegliptin (8p), was chosen for clinical development. Its X-ray structure in complex with the enzyme and early efficacy data in animal models of type 2 diabetes are also presented.

  针对一类基于S1特异性口袋中具有非芳族取代基的氨基苯并[ a ]喹唑啉的DPP-IV抑制剂的设计，合成和SAR进行了描述。选择其代表卡格列汀（8p）进行临床开发。还介绍了其与酶复合的X射线结构以及2型糖尿病动物模型中的早期功效数据。
• Development of a Scalable Synthesis of (<i>S</i>)-3-Fluoromethyl-γ-butyrolactone, Building Block for Carmegliptin’s Lactam Moiety
  作者：Jean-Michel Adam、Joseph Foricher、Steven Hanlon、Bruno Lohri、Gérard Moine、Rudolf Schmid、Helmut Stahr、Martin Weber、Beat Wirz、Ulrich Zutter

  DOI：10.1021/op200019k

  日期：2011.5.20

  Several new routes are reported for the synthesis of (S)-3-fluoromethyl-gamma-butyrolactone. An asymmetric hydrogenation-based synthesis was chosen as the enabling route to produce the lactone on a 10-kg scale. A superior stereoselective route starting from (S)-tert-butyl glycidyl ether which afforded the desired lactone in three steps with similar to 50% overall yield was finally selected for further development and production.