(S)-(2,3-dihydro-2,4,6,7-tetramethylbenzofuran-2-yl)methyl methanesulfonate | 204065-21-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 香豆素
• 英文名称: (S)-(2,3-dihydro-2,4,6,7-tetramethylbenzofuran-2-yl)methyl methanesulfonate
• 英文别名: [(2S)-2,4,6,7-tetramethyl-3H-1-benzofuran-2-yl]methyl methanesulfonate
• CAS: 204065-21-4
• 化学式: C₁₄H₂₀O₄S
• 分子量: 284.376
• InChiKey: NLTZAMWKHOGXTR-AWEZNQCLSA-N

物化性质

• 沸点：
  437.253±34.00 °C(Press: 760.00 Torr)(predicted)
• 密度：
  1.176±0.06 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  61
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-苯基哌啶 、 (S)-(2,3-dihydro-2,4,6,7-tetramethylbenzofuran-2-yl)methyl methanesulfonate 在 potassium carbonate 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 5.0h， 以0.97 g的产率得到(S)-1-<(2,3-dihydro-2,4,6,7-tetramethylbenzofuran-2-yl)methyl>-4-phenylpiperidine
  参考文献：
  名称：

  Synthesis of TAK-218 using (R)-2-methylglycidyl tosylate as a chiral building block

  摘要：

  We performed an asymmetric synthesis of (S)-2,3-dihydro-2,4,6,7-tetramethyl-2-[(4-phenyl-1-piperidinyl)-methyl]-5-benzofuranamine dihydrochloride (TAK-218, 1), a compound used for the treatment of traumatic and ischemic central nervous system injuries. Oxirane 6, which was synthesized from (R)-2-methylglycidyl tosylate, was treated with aqueous trifluoroacetic acid to afford benzofuranmethanol 7 with inversion of stereochemistry at the stereogenic center. Compound 7 was converted into 1 with high enantiomeric excess in four steps. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(99)00138-x
• 作为产物：
  描述：

  2,3,5-三甲基苯酚 在 正丁基锂 、 三氟化硼乙醚 、 溴 、 sodium hydride 、 potassium carbonate 、 叔丁胺 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 为溶剂， 反应 3.08h， 生成 (S)-(2,3-dihydro-2,4,6,7-tetramethylbenzofuran-2-yl)methyl methanesulfonate
  参考文献：
  名称：

  Synthesis of TAK-218 using (R)-2-methylglycidyl tosylate as a chiral building block

  摘要：

  We performed an asymmetric synthesis of (S)-2,3-dihydro-2,4,6,7-tetramethyl-2-[(4-phenyl-1-piperidinyl)-methyl]-5-benzofuranamine dihydrochloride (TAK-218, 1), a compound used for the treatment of traumatic and ischemic central nervous system injuries. Oxirane 6, which was synthesized from (R)-2-methylglycidyl tosylate, was treated with aqueous trifluoroacetic acid to afford benzofuranmethanol 7 with inversion of stereochemistry at the stereogenic center. Compound 7 was converted into 1 with high enantiomeric excess in four steps. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(99)00138-x

文献信息

• US6172085
  申请人：——

  公开号：——

  公开（公告）日：——
• US06172085B2
  申请人：——

  公开号：——

  公开（公告）日：——
• CYCLIC ETHER COMPOUNDS AS SODIUM CHANNEL MODULATORS
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP0923575B1

  公开（公告）日：2003-03-12
• US6172085B1
  申请人：——

  公开号：US6172085B1

  公开（公告）日：2001-01-09
• Synthesis of TAK-218 using (R)-2-methylglycidyl tosylate as a chiral building block
  作者：Kohji Fukatsu、Nobuhiro Fujii、Shigenori Ohkawa

  DOI：10.1016/s0957-4166(99)00138-x

  日期：1999.4

  We performed an asymmetric synthesis of (S)-2,3-dihydro-2,4,6,7-tetramethyl-2-[(4-phenyl-1-piperidinyl)-methyl]-5-benzofuranamine dihydrochloride (TAK-218, 1), a compound used for the treatment of traumatic and ischemic central nervous system injuries. Oxirane 6, which was synthesized from (R)-2-methylglycidyl tosylate, was treated with aqueous trifluoroacetic acid to afford benzofuranmethanol 7 with inversion of stereochemistry at the stereogenic center. Compound 7 was converted into 1 with high enantiomeric excess in four steps. (C) 1999 Elsevier Science Ltd. All rights reserved.