ethyl (3RS)-3-(benzoyloxy)-2,2-difluoro-3-(2,2-dimethyldioxolan-4-yl)propionate | 1010839-84-5

• 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: ethyl (3RS)-3-(benzoyloxy)-2,2-difluoro-3-(2,2-dimethyldioxolan-4-yl)propionate
• 英文别名: ethyl 2,2-difluoro-3-benzoyloxy-3-(2,2-dimethyldioxolan-4-yl)propionate；[1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-3-ethoxy-2,2-difluoro-3-oxopropyl] benzoate
• CAS: 1010839-84-5
• 化学式: C₁₇H₂₀F₂O₆
• 分子量: 358.339
• InChiKey: OMWGKDXWCKGRHY-PZORYLMUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  71.1
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  ethyl (3RS)-3-(benzoyloxy)-2,2-difluoro-3-(2,2-dimethyldioxolan-4-yl)propionate 在 三氟乙酸 水 作用下， 以 乙腈 为溶剂， 反应 6.0h， 生成 Benzoic acid (2R,3R)-4,4-difluoro-2-hydroxymethyl-5-oxo-tetrahydro-furan-3-yl ester
  参考文献：
  名称：

  WO2008/26222

  摘要：

  公开号：
• 作为产物：
  描述：

  (R)-(+)-2,2-二甲基-1,3-二氧戊环-4-甲醛 在 4-二甲氨基吡啶 2,6-二甲基吡啶 、 锌 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 ethyl (3RS)-3-(benzoyloxy)-2,2-difluoro-3-(2,2-dimethyldioxolan-4-yl)propionate
  参考文献：
  名称：

  Stereospecific Synthesis of 2-Deoxy-2,2-difluororibonolactone and Its Use in the Preparation of 2′-Deoxy-2′,2′-difluoro-β-D-ribofuranosyl Pyrimidine Nucleosides: The Key Role of Selective Crystallization

  摘要：

  本文描述了潜在抗癌药物2′-脱氧-2′,2′-二氟胞苷（吉西他滨）的立体特异性合成。通过两次非对映选择性结晶实现了立体选择性：即关键中间体二氟乳糖内酯2a的结晶，以及从异头混合物中结晶出吉西他滨的盐酸盐16b。由于2a可以大量获得，因此合成了其他2′-脱氧-2′,2′-二氟嘧啶核苷，如2′-脱氧-2′,2′-二氟尿苷（19），用于结构-活性关系研究。

  DOI：

  10.1055/s-1992-26167

文献信息

• PROCESS FOR PREPARING GEMCITABINE AND ASSOCIATED INTERMEDIATES
  申请人：Naddaka Vladimir

  公开号：US20070249823A1

  公开（公告）日：2007-10-25

  The present invention provides novel intermediates, which preferably include 3-substituted, alkyl 2,2-difluoro-3-hydroxy-3-(2,2-dialkyldioxolan-4-yl)-propionate derivatives, and 3,5-disubstituted-2-deoxy-2,2-difluoro-1-oxo-D-ribose derivatives. The present invention also provides processes for producing such intermediates and processes for producing gemcitabine therewith.

  本发明提供了新颖的中间体，其中包括3-取代的烷基2,2-二氟-3-羟基-3-(2,2-二烷基二氧杂环戊酮-4-基)-丙酸酯衍生物，以及3,5-二取代-2-脱氧-2,2-二氟-1-氧代-D-核糖衍生物。本发明还提供了生产这种中间体的方法以及生产吉西他滨的方法。
• GEMCITABINE PRODUCTION PROCESS
  申请人：ZELIKOVITCH Lior

  公开号：US20080262215A1

  公开（公告）日：2008-10-23

  Provided is a process for preparing gemcitabine or a salt thereof, which preferably includes selectively precipitating the β-anomer of a 3′,5′-di-O-protected-N 4 -trimethylsilyl-2′-deoxy-2′,2′-difluorocytidine, removing the protecting groups to produce gemcitabine, and, optionally, converting the gemcitabine into a salt. Preferably, the 3′ and 5′ protecting groups are the same or different, and at least one of the 3′ and 5′ protecting groups is cinnamoyl, naphthoyl, naphthylmethylcarbonyl, 2-methylbenzylcarbonyl, 4-methylbenzylcarbonyl or 9-fluorenylmethyloxycarbonyl. Also provided are methods for enriching the β-anomer from an anomeric mixture of a 3′,5′-di-O-protected-N 4 -trimethylsilyl-2′-deoxy-2′,2′-difluorocytidine, e.g., a N 4 -trimethylsilyl-2′-deoxy-2′,2′-difluoro-cytidine-3′,5′-diester, e.g., 3′,5′-dicinnamoyl-N 4 -trimethylsilyl-2′-deoxy-2′,2′-difluorocytidine, using a slurrying process, and methods for converting the β-anomer-enriched product into gemcitabine or a salt thereof.

  提供了一种制备吉西他滨或其盐的过程，其优选包括选择性沉淀3′，5′-二保护-N4-三甲基硅基-2′-脱氧-2′，2′-二氟胞苷的β-异构体，去除保护基以产生吉西他滨，并可将吉西他滨转化为盐。优选地，3′和5′保护基相同或不同，并且3′和5′保护基中至少有一个是肉桂酰基，萘酰基，萘基甲基羰基，2-甲基苄基羰基，4-甲基苄基羰基或9-芴基甲氧羰基。还提供了一种使用搅拌法从3′，5′-二保护-N4-三甲基硅基-2′-脱氧-2′，2′-二氟胞苷的异构体混合物，例如N4-三甲基硅基-2′-脱氧-2′，2′-二氟胞苷-3′，5′-二酯，例如3′，5′-二肉桂酰基-N4-三甲基硅基-2′-脱氧-2′，2′-二氟胞苷，使用混悬过程富集β-异构体的方法，以及将富集β-异构体的产物转化为吉西他滨或其盐的方法。
• Method for the Preparation of D-Erythro-2,2-Difluoro-2-Deoxy-1-Oxoribose Derivative
  申请人：Lee Jaeheon

  公开号：US20080058509A1

  公开（公告）日：2008-03-06

  3R-carboxylate enantiomer derivative of formula (III) can be prepared easily and selectively by the method of the present invention, and a highly pure D-erythro-2,2-difluoro-2-deoxy-1-oxoribose derivative can be prepared efficiently from the compound of formula (III) as an intermediate.
• PROCESS FOR PREPARING OF 2'-DEOXY-2'2'-DIFLUOROCYTIDINE
  申请人：Park Su-Jin

  公开号：US20100069625A1

  公开（公告）日：2010-03-18

  Disclosed is a method for preparing 2′-deoxy-2′,2′-difluorocytidine of Formula I comprising, preparing an optically pure 3R-hydroxypropane amide compound of Formula VIII from an optical ester compound of Formula IX using an optically active chiral amine, preparing an optically pure D-erythro-2,2-difluoro-2-deoxy-1-oxoribose compound of Formula V from the compound of Formula VIII, glycosylating the compound of Formula V with a nucleobase to prepare the 2′-deoxy-2′,2′-difluorocytidine of Formula I as a β-nucleoside. With the present invention, it is possible to prepare an optically pure compound of Formula I in a high purity and a high yield. In the Formulae, R 1 and R 2 are protecting groups and are each independently benzoyl, 4-methylbenzoyl, 3-methylbenzoyl, 4-cyanobenzoyl, 3-cyanobenzoyl, 4-propylbenzoyl, 2-ethoxybenzoyl, 4-t-butylbenzoyl, 1-naphthoyl or 2-naphthoyl, R 3 , R 4 and R 7 are each independently C 1 -C 3 alkyl, R 5 is methyl or ethyl, R 6 is hydrogen, methyl or methoxy.
• US7638642B2
  申请人：——

  公开号：US7638642B2

  公开（公告）日：2009-12-29