(S)-3-(噻吩-2-基硫代)丁酸甲酯 | 133359-79-2

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 中文名称: (S)-3-(噻吩-2-基硫代)丁酸甲酯
• 英文名称: methyl (S)-3-(thiophen-2-ylthio)butyrate
• 英文别名: methyl (S)-3-(2-thienylthio)butyrate；(S)-Methyl 3-(thiophen-2-ylthio)butanoate；methyl (3S)-3-thiophen-2-ylsulfanylbutanoate
• CAS: 133359-79-2
• 化学式: C₉H₁₂O₂S₂
• 分子量: 216.325
• InChiKey: HWLDYKJDDGJZSN-ZETCQYMHSA-N

物化性质

• 沸点：
  307.5±22.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  13
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  79.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-3-(噻吩-2-基硫代)丁酸甲酯 在 盐酸 、 氯磺酸 、 ammonium hydroxide 、 sodium tungstate 、 lithium aluminium tetrahydride 、 dimethyl sulfide borane 、 硫酸 、 双氧水 、 三氟乙酸酐 作用下， 以 四氢呋喃 、 水 、 乙酸乙酯 、 甲苯 为溶剂， 反应 67.5h， 生成 多佐胺-2-6
  参考文献：
  名称：

  An enantioselective synthesis of the topically-active carbonic anhydrase inhibitor MK-0507: 5,6-dihydro-(S)-4-(ethylamino)-(S)-6-methyl-4H-thieno[2,3-b]thiopyran-2-sulfonamide 7,7-dioxide hydrochloride

  摘要：

  The key feature in the synthesis of topically-active carbonic anhydrase inhibitor MK-0507 (13b) is a Ritter reaction that exhibits an unexpected tendency to proceed with retention of chirality. This phenomenon was further studied on model compounds free from potential diastereomeric effects. A mechanism involving transannular stabilization of the sp2-hybridized center by sulfone oxygen is proposed with the net result of double inversion. A second key feature in the preferred sequence to MK-0507 involves the classic problem of how to maximize substitution over elimination. This problem manifests itself in the stereospecific alkylation of 2-mercaptothiophene with derivatized methyl (R)-3-hydroxybutyrate and is compounded by a subsequent Michael reaction leading to a loss of product chirality. Results are presented that eliminate this problem.

  DOI：

  10.1021/jo00059a013
• 作为产物：
  描述：

  (R)-3-羟基丁酸甲酯 在 吡啶 作用下， 以 四氢呋喃 、 formamide 为溶剂， 反应 96.0h， 生成 (S)-3-(噻吩-2-基硫代)丁酸甲酯
  参考文献：
  名称：

  An enantioselective synthesis of the topically-active carbonic anhydrase inhibitor MK-0507: 5,6-dihydro-(S)-4-(ethylamino)-(S)-6-methyl-4H-thieno[2,3-b]thiopyran-2-sulfonamide 7,7-dioxide hydrochloride

  摘要：

  The key feature in the synthesis of topically-active carbonic anhydrase inhibitor MK-0507 (13b) is a Ritter reaction that exhibits an unexpected tendency to proceed with retention of chirality. This phenomenon was further studied on model compounds free from potential diastereomeric effects. A mechanism involving transannular stabilization of the sp2-hybridized center by sulfone oxygen is proposed with the net result of double inversion. A second key feature in the preferred sequence to MK-0507 involves the classic problem of how to maximize substitution over elimination. This problem manifests itself in the stereospecific alkylation of 2-mercaptothiophene with derivatized methyl (R)-3-hydroxybutyrate and is compounded by a subsequent Michael reaction leading to a loss of product chirality. Results are presented that eliminate this problem.

  DOI：

  10.1021/jo00059a013

文献信息

• 一种盐酸多佐胺关键中间体的简易合成方法
  申请人：株洲壹诺生物技术有限公司

  公开号：CN110128441A

  公开（公告）日：2019-08-16

  本发明公开了一种盐酸多佐胺关键中间体的简易合成方法，所述盐酸多佐胺关键中间体的简易合成方法包括以下步骤：化合物Ⅱ在酸性催化剂作用下，发生分子内关环反应生成初产品；对初产品进行淬灭处理，再萃取、浓缩有机相得粗产品；将粗产品进行重结晶、过滤、干燥得所述盐酸多佐胺关键中间体。本发明的有益效果为：本发明所述一种盐酸多佐胺关键中间体的合成方法比较简单，一步合成，且生成的产物化合物Ⅰ的产率比较高，产品纯度较高，相对于传统的合成方法，本发明所述一种盐酸多佐胺关键中间体的合成方法节省了原料成本，且所生成的产物的纯度较高，提高了产物的利用率。
• Enantioselective Michael additions on α,β-unsaturated N-acylated oxazolidin-2-ones using mild scandium triflate catalysis
  作者：Sami J.K. Sauerland、Eero Kiljunen、Ari M.P. Koskinen

  DOI：10.1016/j.tetlet.2005.12.076

  日期：2006.2

  The asymmetric conjugate addition of thiophenol to (E)-3-crotonoyloxazolidin-2-one catalysed by the scandium(III) triflate complex of Ph-PYBOX gave the corresponding adduct in 66% ee. Lanthanoid triflates gave lower enantioselectivities (⩽28% ee).

  Ph-PYBOX的三氟甲磺酸complex（III）络合物催化将苯硫酚不对称地加到（E）-3-巴豆酰恶唑烷丁二酮-2-酮上，得到66％ee的相应加合物。镧系三氟甲磺酸酯具有较低的对映选择性（⩽28％ee）。
• (S)-Alkyl 3-(thien-2-ylthio)butyrate and analogs and synthesis thereof
  申请人：Merck & Co., Inc.

  公开号：US04968814A1

  公开（公告）日：1990-11-06

  (S)-Alkyl 3-(thien-2-ylthio)butyrate and analogs are intermediates in the synthesis of the chiral (S,S)-5,6-dihydro-4-ethylamino-6-methyl-4H-thieno[2,3-b]thiopyran-2-sulfon amide-7,7-dioxide and analogs thereof, topically effective carbonic anhydrase inhibitors useful in the treatment of ocular hypertension and glaucoma.

  (S)-烷基3-(噻吩-2-硫基)丁酸酯及其类似物是手性(S,S)-5,6-二氢-4-乙基氨基-6-甲基-4H-噻吩[2,3-b]硫杂吡喃-2-磺酰胺-7,7-二氧化物及其类似物的合成中间体，这些化合物是局部有效的碳酸酐酶抑制剂，可用于治疗眼压和青光眼。
• J. Org. Chem. 1993,58, 1672-1679
  作者：

  DOI：——

  日期：——
• An enantioselective synthesis of the topically-active carbonic anhydrase inhibitor MK-0507: 5,6-dihydro-(S)-4-(ethylamino)-(S)-6-methyl-4H-thieno[2,3-b]thiopyran-2-sulfonamide 7,7-dioxide hydrochloride
  作者：Thomas J. Blacklock、Paul Sohar、John W. Butcher、T. Lamanec、E. J. J. Grabowski

  DOI：10.1021/jo00059a013

  日期：1993.3

  The key feature in the synthesis of topically-active carbonic anhydrase inhibitor MK-0507 (13b) is a Ritter reaction that exhibits an unexpected tendency to proceed with retention of chirality. This phenomenon was further studied on model compounds free from potential diastereomeric effects. A mechanism involving transannular stabilization of the sp2-hybridized center by sulfone oxygen is proposed with the net result of double inversion. A second key feature in the preferred sequence to MK-0507 involves the classic problem of how to maximize substitution over elimination. This problem manifests itself in the stereospecific alkylation of 2-mercaptothiophene with derivatized methyl (R)-3-hydroxybutyrate and is compounded by a subsequent Michael reaction leading to a loss of product chirality. Results are presented that eliminate this problem.