(2S)-1-(2,4-difluorophenyl)-3-hydroxy-2-methylpropan-1-one | 170862-57-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2S)-1-(2,4-difluorophenyl)-3-hydroxy-2-methylpropan-1-one
• CAS: 170862-57-4
• 化学式: C₁₀H₁₀F₂O₂
• 分子量: 200.185
• InChiKey: FSUUOZPBWRTXGH-LURJTMIESA-N

物化性质

• 沸点：
  302.3±32.0 °C(Predicted)
• 密度：
  1.248±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  氯甲基二甲基异丙氧基硅烷 、 (2S)-1-(2,4-difluorophenyl)-3-hydroxy-2-methylpropan-1-one 在 magnesium 作用下， 以 四氢呋喃 、 1,2-二溴乙烷 为溶剂， 反应 0.75h， 生成 (4R,5S)-4-(2,4-difluorophenyl)-2,2,5-trimethyl-1,2-oxasilinan-4-ol
  参考文献：
  名称：

  Carbon analogs of antifungal dioxane-triazole derivatives: Synthesis and in vitro activities

  摘要：

  A new series of triazole compounds possessing a carbon atom in place of a sulfur atom were efficiently synthesized and their in vitro antifungal activities were investigated. The carbon analogs showed excellent in vitro activity against Candida, Cryptococcus, and Aspergillus species. The MICs of compound 1c against C. albicans ATCC24433, C. neoformans TIMM1855, and A. fumigatus ATCC26430 were 0.016, 0.016, and 0.125 mu g/mL, respectively (MICs of fluconazole: 0.5, >4, and >4 mu g/mL; MICs of itraconazole: 0.125, 0.25, and 0.25 mu g/mL). (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.10.055
• 作为产物：
  描述：

  (2S)-1-(2,4-difluorophenyl)-2-methyl-3-trityloxypropan-1-one 在 对甲苯磺酸 作用下， 以 甲醇 为溶剂， 反应 0.33h， 以58%的产率得到(2S)-1-(2,4-difluorophenyl)-3-hydroxy-2-methylpropan-1-one
  参考文献：
  名称：

  A Novel Route for Chiral Synthesis of the Triazole Antifungal ER-30346.

  摘要：

  开发了一种新的合成路线，以市售的手性化合物甲基S-(+)-3-羟基-2-甲基丙酸酯为原料，制备口服活性三唑类抗真菌药物ER-30346的关键中间体(2S, 3S)-2-(2, 4-二氟苯基)-3-羟基-2-甲基-4-(1-(1, 2, 4-三唑基))丁腈(2)。通过四氧化锇催化的双羟基化反应，以6.4 : 1的非对映选择性构建了第二个手性中心。

  DOI：

  10.1248/cpb.46.1125

文献信息

• Azole antifungal agents, processes for the preparation thereof, and intermediates
  申请人：Eisai Co., Ltd.

  公开号：EP1231210A2

  公开（公告）日：2002-08-14

  A compound represented by the general formula: wherein R1 and R2 denote a halogen atom or hydrogen atoms; R3 means a hydrogen atoms or lower alkyl group; r and m stand for 0 or 1; A is N or CH; W denotes an aromatic ring or a condensed ring thereof; X means another aromatic rings, an alkanediyl group, an alkenediyl group, or an alkynediyl group; Y stand for -S-, etc.; Z denotes a hydrogen atom, etc., or a salt thereof, and intermediates thereof or a salt thereof as well as processes for the preparation thereof, and pharmacetical composition suitable for use as an antifungal agent.

  通用公式表示的化合物为： 其中R1和R2表示卤素原子或氢原子；R3表示氢原子或较低的烷基基团；r和m代表0或1；A为N或CH；W表示芳香环或其缩合环；X表示另一个芳香环、烷二基基团、烯二基基团或炔二基基团；Y代表-S-等；Z表示氢原子等，或其盐，以及其中间体或其盐，以及用作抗真菌剂的制备方法和适用的药物组合物。
• A Novel Route for Chiral Synthesis of the Triazole Antifungal ER-30346.
  作者：Yumiko KAKU、Akihiko TSURUOKA、Hiroyuki KAKINUMA、Itaru TSUKADA、Manabu YANAGISAWA、Toshihiko NAITO

  DOI：10.1248/cpb.46.1125

  日期：——

  A novel synthetic route to (2S, 3S)-2-(2, 4-difluorophenyl)-3-hydroxy-2-methyl-4-(1-(1, 2, 4-triazolyl))butyronitrile (2), an intermediate for the orally active triazole antifungal agent ER-30346, was developed from methyl S-(+)-3-hydroxy-2-methylpropionate, a commercially available chiral compound. The second chiral center was constructed with 6.4 : 1 diastereoselectivity via osmium tetroxide catalyzed dihydroxylation.

  开发了一种新的合成路线，以市售的手性化合物甲基S-(+)-3-羟基-2-甲基丙酸酯为原料，制备口服活性三唑类抗真菌药物ER-30346的关键中间体(2S, 3S)-2-(2, 4-二氟苯基)-3-羟基-2-甲基-4-(1-(1, 2, 4-三唑基))丁腈(2)。通过四氧化锇催化的双羟基化反应，以6.4 : 1的非对映选择性构建了第二个手性中心。
• Carbon analogs of antifungal dioxane-triazole derivatives: Synthesis and in vitro activities
  作者：Takuya Uchida、Atsushi Somada、Yoshiko Kagoshima、Toshiyuki Konosu、Sadao Oida

  DOI：10.1016/j.bmcl.2008.10.055

  日期：2008.12

  A new series of triazole compounds possessing a carbon atom in place of a sulfur atom were efficiently synthesized and their in vitro antifungal activities were investigated. The carbon analogs showed excellent in vitro activity against Candida, Cryptococcus, and Aspergillus species. The MICs of compound 1c against C. albicans ATCC24433, C. neoformans TIMM1855, and A. fumigatus ATCC26430 were 0.016, 0.016, and 0.125 mu g/mL, respectively (MICs of fluconazole: 0.5, >4, and >4 mu g/mL; MICs of itraconazole: 0.125, 0.25, and 0.25 mu g/mL). (C) 2008 Elsevier Ltd. All rights reserved.