O-2,5-difluorophenyl N,N-diethylcarbamate | 1207163-57-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: O-2,5-difluorophenyl N,N-diethylcarbamate
• 英文别名: 2,5-Difluorophenyl diethylcarbamate；(2,5-difluorophenyl) N,N-diethylcarbamate
• CAS: 1207163-57-2
• 化学式: C₁₁H₁₃F₂NO₂
• mdl: MFCD25956562
• 分子量: 229.227
• InChiKey: HJHJYOTXLKTQJZ-UHFFFAOYSA-N

物化性质

• 沸点：
  273.4±40.0 °C(Predicted)
• 密度：
  1.192±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.363
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  O-2,5-difluorophenyl N,N-diethylcarbamate 在 仲丁基锂 、 氘代甲醇 作用下， 以 四氢呋喃 为溶剂， 反应 1.83h， 以76%的产率得到O-2-deuterio-3,6-difluorophenyl N,N-diethylcarbamate
  参考文献：
  名称：

  O-(3,n-二卤苯基)N,N-二乙基氨基甲酸酯的邻位锂化反应：二卤代水杨酰胺和 2,3,n-三卤苯酚衍生物的合成

  摘要：

  通过使用定向邻位金属化 (DoM) 策略，从容易获得的 O-(3,n-二卤苯基) N,N-二乙基氨基甲酸酯合成了新的二卤水杨酰胺和三卤苯酚衍生物。与 sBuLi 的邻锂化反应在双重活化的 C-2 位置区域选择性地发生，这证明了 O-氨基甲酸酯作为定向金属化基团的能力。此外，通过使用串联转腈/SNAr 反应序列从有机锂中间体获得高度官能化的芳腈。

  DOI：

  10.1002/ejoc.201600933
• 作为产物：
  描述：

  2,5-二氟苯酚 、 N,N-二乙基氯甲酰胺 在 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 24.17h， 以92%的产率得到O-2,5-difluorophenyl N,N-diethylcarbamate
  参考文献：
  名称：

  O-(3,n-二卤苯基)N,N-二乙基氨基甲酸酯的邻位锂化反应：二卤代水杨酰胺和 2,3,n-三卤苯酚衍生物的合成

  摘要：

  通过使用定向邻位金属化 (DoM) 策略，从容易获得的 O-(3,n-二卤苯基) N,N-二乙基氨基甲酸酯合成了新的二卤水杨酰胺和三卤苯酚衍生物。与 sBuLi 的邻锂化反应在双重活化的 C-2 位置区域选择性地发生，这证明了 O-氨基甲酸酯作为定向金属化基团的能力。此外，通过使用串联转腈/SNAr 反应序列从有机锂中间体获得高度官能化的芳腈。

  DOI：

  10.1002/ejoc.201600933

文献信息

• 1,5-O → N Carbamoyl Snieckus–Fries-Type Rearrangement
  作者：Claudia Feberero、Samuel Suárez-Pantiga、Zaida Cabello、Roberto Sanz

  DOI：10.1021/acs.orglett.8b00782

  日期：2018.4.20

  The reaction of o-lithiated O-aryl N,N-diethylcarbamates with (hetero)aromatic nitriles gives rise to functionalized salicylidene urea derivatives in high yields through a new 1,5-O → N carbamoyl migration. This Snieckus–Fries-type rearrangement nicely complements previously known O → C and O → O related shifts. In addition, when dimethylmalononitrile is used as the electrophilic partner, the carbamoyl

  的反应ö -lithiated ø -芳基N，N- -diethylcarbamates与（杂）芳族腈通过一个新的1,5- O→Ñ氨基甲酰基迁移引起高收率官能亚水杨脲衍生物。这种Snieckus–Fries类型的重排很好地补充了先前已知的O→C和O→O相关的移位。另外，当使用二甲基丙二腈作为亲电子伴侣时，相对于预期的硝化反应，氨基甲酰基转移是优选的。
• Transition Metal-Free Synthesis of Halobenzo[b]furans from O-Aryl Carbamates via o-Lithiation Reactions
  作者：Claudia Feberero、Cintia Virumbrales、Carlos Sedano、Lorena Renedo、Samuel Suárez-Pantiga、Roberto Sanz

  DOI：10.3390/molecules27020525

  日期：——

  A straightforward and transition metal-free one-pot protocol to synthesize halobenzo[b]furans has been developed employing simple and easily available starting materials such as O-aryl carbamates and alkynylsulfones. The fine-tuning of the different steps involved was key to achieving a successful one-pot procedure. Initially, a directed ortho-lithiation process, which uses the carbamate as the directed

  使用简单易得的起始材料（如 O-芳基氨基甲酸酯和炔基砜）开发了一种直接且不含过渡金属的一锅法合成卤代苯并 [b] 呋喃。所涉及的不同步骤的微调是成功实现一锅法的关键。最初，使用氨基甲酸酯作为定向金属化基团的定向邻位锂化过程对于通过邻锂化氨基甲酸酯的直接炔基化提供 O-2-炔基芳基 N,N-二乙基氨基甲酸酯至关重要，芳基磺酰基炔烃作为亲电试剂。通过涉及在常规加热或微波照射下原位氨基甲酸酯碱水解的策略，成功地完成了生成的邻炔基氨基甲酸酯的环化，再加上随后的杂环化步骤，提供所需的苯并[b]呋喃。已经合成了多种新的卤代苯并[b]呋喃，并通过进一步转化证明了它们的实用性。
• Novel spiropiperidine-based stearoyl-CoA desaturase-1 inhibitors: Identification of 1′-{6-[5-(pyridin-3-ylmethyl)-1,3,4-oxadiazol-2-yl]pyridazin-3-yl}-5-(trifluoromethyl)-3,4-dihydrospiro[chromene-2,4′-piperidine]
  作者：Yoshikazu Uto、Yohei Kiyotsuka、Yuko Ueno、Yuriko Miyazawa、Hitoshi Kurata、Tsuneaki Ogata、Tsuneo Deguchi、Makiko Yamada、Nobuaki Watanabe、Masahiro Konishi、Nobuya Kurikawa、Toshiyuki Takagi、Satoko Wakimoto、Keita Kono、Jun Ohsumi

  DOI：10.1016/j.bmcl.2009.11.043

  日期：2010.1

  Cyclization of the benzoylpiperidine in lead compound 2 generated a series of novel and highly potent spiropiperidine-based stearoyl-CoA desaturase (SCD)-1 inhibitors. Among them, 1'-6-[5-(pyridin-3-ylmethyl)-1,3,4-oxadiazol-2-yl]pyridazin-3-yl}-5-(trifluoromethyl)-3,4-dihydrospiro[chromene-2,4'-piperidine] (19) demonstrated the most powerful inhibitory activity against SCD-1, not only in vitro but also in vivo (C57BL/6 J mice). With regard to the pharmacological evaluation, 19 showed powerful reduction of the desaturation index in the plasma of C57BL/6 J mice on a non-fat diet after a 7-day oral administration (q.d.) without causing notable abnormalities in the eyes or skin up to the highest dose (3 mg/kg) in our preliminary analysis. (C) 2009 Elsevier Ltd. All rights reserved.
• Synthesis and evaluation of novel stearoyl-CoA desaturase 1 inhibitors: 1′-{6-[5-(pyridin-3-ylmethyl)-1,3,4-oxadiazol-2-yl]pyridazin-3-yl}-3,4-dihydrospiro[chromene-2,4′-piperidine] analogs
  作者：Yoshikazu Uto、Yuko Ueno、Yohei Kiyotsuka、Yuriko Miyazawa、Hitoshi Kurata、Tsuneaki Ogata、Makiko Yamada、Tsuneo Deguchi、Masahiro Konishi、Toshiyuki Takagi、Satoko Wakimoto、Jun Ohsumi

  DOI：10.1016/j.ejmech.2010.07.044

  日期：2010.11

  In continuation of our investigation on novel stearoyl-CoA desaturase (SCD) 1 inhibitors, we have already reported on the structural modification of the benzoylpiperidines that led to a series of novel and highly potent spiropiperidine-based SCD1 inhibitors. In this report, we would like to extend the scope of our previous investigation and disclose details of the synthesis, SAR, ADME, PK, and pharmacological evaluation of the spiropiperidines with high potency for SCD1 inhibition. Our current efforts have culminated in the identification of 5-fluoro-1'-6-[5-(pyridin-3-ylmethyl)-1,3,4-oxadiazol-2-yl]pyridazin-3-yl}-3,4-dihydrospiro[chromene-2,4'-piperidine] (10e), which demonstrated a very strong potency for liver SCD1 inhibition (ID(50) = 0.6 mg/kg). This highly efficacious inhibition is presumed to be the result of a combination of strong enzymatic inhibitory activity (IC(50) (mouse)= 2 nM) and good oral bioavailability (F >95%). Pharmacological evaluation of 10e has demonstrated potent, dose-dependent reduction of the plasma desaturation index in C57BL/6J mice on a high carbohydrate diet after a 7-day oral administration (q.d.). In addition, it did not cause any noticeable skin abnormalities up to the highest dose (10 mg/kg). (C) 2010 Elsevier Masson SAS. All rights reserved.
• Experimental and Computational Study of the 1,5-O → N Carbamoyl Snieckus–Fries-Type Rearrangement
  作者：Claudia Feberero、Carlos Sedano、Samuel Suárez-Pantiga、Carlos Silva López、Roberto Sanz

  DOI：10.1021/acs.joc.0c01732

  日期：2020.10.2

  The reactions of o-lithiated O-aryl N,N-diethylcarbamates with different C–N multiple bond electrophiles have been thoroughly studied. A 1,5-O → N carbamoyl shift, a new variation of the anionic Fries-type rearrangement, takes place when nitriles, imines, or alkylcarbodiimides are employed. In these cases, the carbamoyl group plays a dual role as a directing group, building up a variety of functional

  彻底研究了O-锂化的O-芳基N，N-二乙基氨基甲酸酯与不同的C-N多键亲电试剂的反应。当使用腈，亚胺或烷基碳二亚胺时，会发生1，5-O→N的氨基甲酰基转移，这是阴离子Fries型重排的新变化。在这些情况下，氨基甲酰基起着指导基团的双重作用，通过1，5-O→N氨基甲酰基的迁移建立了各种官能团。另一方面，使用异（硫）氰酸酯和芳基碳二亚胺导致未重排的o-官能化O-芳基氨基甲酸酯。这种反应性在计算上得到了进一步的探索，其控制因素可以追溯到替代产品的相对碱性（迁移或未迁移的底物）。这项探索还提供了有关锂阳离子在这些基材上的络合程度的有趣见解。还已经开发出有用的2-羟基二苯甲酮衍生物的新途径。