(2R)-1-chloro-3-[(4-morpholin-4-yl-1,2,5-thiadiazol-3-yl)oxy]propan-2-ol | 935528-00-0

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (2R)-1-chloro-3-[(4-morpholin-4-yl-1,2,5-thiadiazol-3-yl)oxy]propan-2-ol
• CAS: 935528-00-0
• 化学式: C₉H₁₄ClN₃O₃S
• 分子量: 279.747
• InChiKey: DDMMUKVUEJQEPV-ZETCQYMHSA-N

物化性质

• 沸点：
  471.9±45.0 °C(Predicted)
• 密度：
  1.434±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  96
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2R)-1-chloro-3-[(4-morpholin-4-yl-1,2,5-thiadiazol-3-yl)oxy]propan-2-ol 在 potassium tert-butylate 、 potassium iodide 作用下， 以 四氢呋喃 为溶剂， 反应 74.0h， 生成 马来酸噻吗洛尔
  参考文献：
  名称：

  Enantioselective synthesis of (S)-timolol via kinetic resolution of terminal epoxides and dihydroxylation of allylamines

  摘要：

  An efficient enantioselective synthesis of (S)-timolol has been described using chiral Co-salen-catalyzed kinetic resolution of less expensive (+/-)-epichlorohydrin with 3-hydroxy-4-(N-morpholino)-1,2,5-thiadiazole in good overall yield (55%) and excellent enantioselectivity (98%). Synthesis of (S)-timolol has also been achieved using hydrolytic kinetic resolution as well as asymmetric dihydroxylation routes in 90% ee and 56% ee, respectively. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2007.01.057
• 作为产物：
  描述：

  4-吗啉-4-基-1,2,5-三唑-3-酮 、 环氧氯丙烷 在 (R,R)-(salen)Co[OC(CF₃)3] 作用下， 以 various solvent(s) 为溶剂， 反应 12.0h， 以86%的产率得到(2R)-1-chloro-3-[(4-morpholin-4-yl-1,2,5-thiadiazol-3-yl)oxy]propan-2-ol
  参考文献：
  名称：

  Enantioselective synthesis of (S)-timolol via kinetic resolution of terminal epoxides and dihydroxylation of allylamines

  摘要：

  An efficient enantioselective synthesis of (S)-timolol has been described using chiral Co-salen-catalyzed kinetic resolution of less expensive (+/-)-epichlorohydrin with 3-hydroxy-4-(N-morpholino)-1,2,5-thiadiazole in good overall yield (55%) and excellent enantioselectivity (98%). Synthesis of (S)-timolol has also been achieved using hydrolytic kinetic resolution as well as asymmetric dihydroxylation routes in 90% ee and 56% ee, respectively. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2007.01.057

文献信息

• Biocatalytic Asymmetric Synthesis of (<i>S</i>)- and (<i>R</i>)-Timolol
  作者：Fabio Prati、Giovanni Tosi、Federica Zironi、Emilia Caselli、Arrigo Forni

  DOI：10.1055/s-2004-822395

  日期：——

  A new biocatalytic route for the synthesis of both enantiomers of Timolol (1) is described. Starting from 3,4-dichloro1,2,5-thiadiazole (2), (R)- and (S)-Timolol (87% ee) were obtained in 35% and 30% overall yield, respectively. Asymmetric reduction of the intermediate haloketone 5 with baker's yeast afforded the corresponding halohydrin 6 in the optically active form (87% ee), which gave the R enantiomer

  描述了合成噻吗洛尔 (1) 的两种对映异构体的新生物催化途径。从 3,4-二氯 1,2,5-噻二唑 (2) 开始，(R)- 和 (S)-噻吗洛尔 (87% ee) 分别以 35% 和 30% 的总产率获得。用面包酵母不对称还原中间体卤代酮5，得到光学活性形式的相应卤代醇6（87% ee），得到噻吗洛尔的R对映异构体（二异构体）。S 对映异构体 (eutomer) 是通过在 Mitsunobu 程序后反转卤代醇的构型获得的。