tert-butyl 3-(2,4-dioxothiazolidin-3-yl)-4-fluoropiperidine-1-carboxylate | 1548129-41-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: tert-butyl 3-(2,4-dioxothiazolidin-3-yl)-4-fluoropiperidine-1-carboxylate
• CAS: 1548129-41-4
• 化学式: C₁₃H₁₉FN₂O₄S
• 分子量: 318.369
• InChiKey: AJRXJOXJITUTIB-UHFFFAOYSA-N

物化性质

• 沸点：
  418.5±55.0 °C(predicted)
• 密度：
  1.34±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.03
• 重原子数：
  21.0
• 可旋转键数：
  1.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  66.92
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  N-BOC-1,2,3,6-四氢吡啶 在 magnesium(II) perchlorate 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 60.3h， 生成 tert-butyl 4-(2,4-dioxothiazolidin-3-yl)-3-fluoropiperidine-1-carboxylate 、 tert-butyl 3-(2,4-dioxothiazolidin-3-yl)-4-fluoropiperidine-1-carboxylate
  参考文献：
  名称：

  Process Development for Scale-Up of a Novel 3,5-Substituted Thiazolidine-2,4-dione Compound as a Potent Inhibitor for Estrogen-Related Receptor 1

  摘要：

  The development of a reproducible process for multihundred gram production of (Z)-5-((1-(4-chloro-2-(trifluoromethyl)benzyl)-1H-indazol-5-yl)methylene)-3-((3R,4R)-3-fluoro-1-methylpiperidin-4-yl)thiazolidine-2,4-dione (26), a potent and selective inhibitor of estrogen-related receptor 1 (ERR!), is described. This multihundred gram synthesis was achieved via magnesium perchlorate-catalyzed regioselective epoxide ring-opening of tert-butyl 7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxylate (9) with thiazolidine-2,4-dione (6, TZD) to form a diastereomeric mixture tert-butyl 4-(2,4-dioxothiazolidin-3-yl)-3-hydroxypiperidine-1-carboxylate (17), of which the 3-hydroxyl group was functionally transformed to 3-fluoro derivative 19 after treatment with Deoxo-Fluor. Chiral separation of 19 provided the desired diastereomer (3R,4R)-21 that was converted to the secondary amine 23 TFA salt. Reductive amination of 23 produced the key intermediate N-methyl 24. Knoevenagel condensation of 24 with 1-(4-chloro-2-(trifluoromethyl)benzyl)-1H-indazole-5-carbaldehyde (5) produced the final product 26 in 10% overall yield (99.7% HPLC area% with >= 99.5% de) after a convergent eight synthetic steps with the only column purification being the chiral HPLC separation of 3R,4R-21 from 3S,4S-22.

  DOI：

  10.1021/op400325r