ethyl (Z)-2-(chroman-4-ylidene)acetate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: ethyl (Z)-2-(chroman-4-ylidene)acetate
• 英文别名: ethyl (E,Z)-(3,4-dihydro-2H-1-benzopyran-4-ylidene)acetate；chroman-(4Z)-ylidene-acetic acid ethyl ester；ethyl (2Z)-2-(2,3-dihydrochromen-4-ylidene)acetate
• 化学式: C₁₃H₁₄O₃
• 分子量: 218.252
• InChiKey: ZUPWDLFUXLMICR-KTKRTIGZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl (Z)-2-(chroman-4-ylidene)acetate 在 4-碘甲苯 、 Olah′s reagent 、 triethylamine tris(hydrogen fluoride) 、 间氯过氧苯甲酸 作用下， 以 氯仿 为溶剂， 以58 %的产率得到ethyl 4,4-difluoro-2,3,4,5-tetrahydrobenzo[b]oxepine-5-carboxylate
  参考文献：
  名称：

  Catalytic Ring Expanding Difluorination: An Enantioselective Platform to Access β,β‐Difluorinated Carbocycles

  摘要：

  Cyclic β,β‐difluoro‐carbonyl compounds have a venerable history as drug discovery leads, but limitations in the synthesis arsenal continue to impede chemical space exploration. This challenge is particularly acute in the arena of fluorinated medium rings where installing the difluoromethylene unit subtly alters the ring conformation by expanding the internal angle (∠C−CF₂−C>∠C−CH₂−C): this provides a handle to modulate physicochemistry (e.g. pK_a). To reconcile this disparity, a highly modular ring expansion has been devised that leverages simple α,β‐unsaturated esters and amides, and processes them to one‐carbon homologated rings with concomitant geminal difluorination (6 to 10 membered rings, up to 95 % yield). This process is a rare example of the formal difluorination of an internal alkene and is enabled by sequential I(III)‐enabled O‐activation. Validation of enantioselective catalysis in the generation of unprecedented medium ring scaffolds is reported (up to 93 : 7 e.r.) together with X‐ray structural analyses and product derivatization.

  DOI：

  10.1002/anie.202403957
• 作为产物：
  描述：

  2,3-二氢苯并吡喃-4-酮 、 triethyl phosphonoacetic acid 以 四氢呋喃 为溶剂， 生成 ethyl (Z)-2-(chroman-4-ylidene)acetate
  参考文献：
  名称：

  Benzopyran derivatives, their preparation and pharmaceutical

  摘要：

  通用公式（I）的新苯并吡喃衍生物，其中：R.sub.1代表氢或卤素原子或羟基、烷氧基、硝基、氨基、烷基磺酰胺基或酰胺基基团，R代表（1）基团：R.sub.2和R.sub.3可以相同也可以不同，分别为H、卤素、OH、烷基、烷氧基、NH.sub.2、烷基磺酰胺基或NO.sub.2，或（2）基团：n为0或1，R.sub.4为H、烷基或可选择性取代的苯基，Q为酰基、烷基磺酰基或Y为--CO--或--SO.sub.2--，Z为单键、--CH.sub.2--或--NH--，或（3）基团：n为0或1，m为0或2，X为C或N（如果n=0），W为键或--NH--，AR为吡啶基、吲哚基、喹啉基、2-烷基喹啉基或苯基，可选择性取代R.sub.2和R.sub.3，但当X等于N时，n=0，或（4）基团的一般公式：R.sub.7为H或烷基，或者（5）基团：R'和R"相同，分别代表氢原子或烷基基团，它们的异构形式和混合物，以及其与酸的加合盐。这些新产品可用作抗心律失常和抗纤颤剂。

  公开号：

  US05025013A1

文献信息

• Benzopyran derivatives, their preparation and pharmaceutical
  申请人：Rhone-Poulenc Sante

  公开号：US05025013A1

  公开（公告）日：1991-06-18

  New benzopyran derivatives of general formula (I) in which: R.sub.1 represents a hydrogen or halogen atom or a hydroxy, alkyloxy, nitro, amino, alkylsulphonamido or acylamino radical, R represents (1) radical ##STR1## R.sub.2 and R.sub.3, which may be identical or different, being H, halogen, OH, alkyl, alkyloxy, NH.sub.2, alkylsulphonamido or NO.sub.2, or (2) a radical ##STR2## n being 0 or 1, R.sub.4 being H, alkyl or optionally substituted phenyl and Q is acyl, alkylsulphonyl or ##STR3## Y being --CO-- or --SO.sub.2 -- and Z being a single bond, --CH.sub.2 -- or --NH--, or (3) a radical ##STR4## n being 0 or 1, m being 0 or 2, X being C or N (if n=0), W being a bond or --NH-- and AR being pyridyl, indolyl, quinolyl, 2-alkylquinolyl or phenyl optionally substituted with R.sub.2 and R.sub.3, provided that n=0 when X equals N, or (4) a radical of general formula: ##STR5## R.sub.7 being H or alkyl, or alternatively (5) a radical ##STR6## R' and R" are identical and represent hydrogen atoms or alkyl radicals, their isomeric forms and the mixtures thereof, and their addition salts with acids. These new products are useful as anti-arrhythmic and antifibrillating agents. ##STR7##

  通用公式（I）的新苯并吡喃衍生物，其中：R.sub.1代表氢或卤素原子或羟基、烷氧基、硝基、氨基、烷基磺酰胺基或酰胺基基团，R代表（1）基团：R.sub.2和R.sub.3可以相同也可以不同，分别为H、卤素、OH、烷基、烷氧基、NH.sub.2、烷基磺酰胺基或NO.sub.2，或（2）基团：n为0或1，R.sub.4为H、烷基或可选择性取代的苯基，Q为酰基、烷基磺酰基或Y为--CO--或--SO.sub.2--，Z为单键、--CH.sub.2--或--NH--，或（3）基团：n为0或1，m为0或2，X为C或N（如果n=0），W为键或--NH--，AR为吡啶基、吲哚基、喹啉基、2-烷基喹啉基或苯基，可选择性取代R.sub.2和R.sub.3，但当X等于N时，n=0，或（4）基团的一般公式：R.sub.7为H或烷基，或者（5）基团：R'和R"相同，分别代表氢原子或烷基基团，它们的异构形式和混合物，以及其与酸的加合盐。这些新产品可用作抗心律失常和抗纤颤剂。
• Ir-Catalyzed Asymmetric Allylic Alkylation of Dialkyl Malonates Enabling the Construction of Enantioenriched All-Carbon Quaternary Centers
  作者：Farbod A. Moghadam、Elliot F. Hicks、Zachary P. Sercel、Alexander Q. Cusumano、Michael D. Bartberger、Brian M. Stoltz

  DOI：10.1021/jacs.2c02960

  日期：2022.5.11

  An enantioselective iridium-catalyzed allylic alkylation of malonates with trisubstituted allylic electrophiles to form all-carbon quaternary stereocenters is reported. This reaction proceeds at ambient temperature and enables the preparation of a wide range of enantioenriched products in up to 93% yield and 97% ee. The quaternary products can be readily converted to several valuable building blocks

  报道了丙二酸酯与三取代的烯丙基亲电子试剂形成全碳季立构中心的对映选择性铱催化的烯丙基烷基化。该反应在环境温度下进行，能够以高达 93% 的产率和 97% 的 ee 制备范围广泛的对映体富集产品。季产品可以很容易地转化为几种有价值的结构单元，例如邻位季产品和 β-季酸。
• Heterocyclyl derivatives and their use as prostaglandin D2 receptor modulators
  申请人：Actelion Pharmaceuticals Ltd.

  公开号：US09255090B2

  公开（公告）日：2016-02-09

  The present invention relates to phenyl-substituted heterocyclyl derivatives of the formula (I), wherein Z, n, m, R1, R2, R3, R4, R5, R6, R7 and R8 are as described in the description and their use as prostaglandin receptor modulators, most particularly as prostaglandin D2 receptor modulators, in the treatment of various prostaglandin-mediated diseases and disorders, to pharmaceutical compositions containing these compounds and to processes for their preparation.

  本发明涉及公式（I）的苯基取代的杂环基衍生物，其中Z，n，m，R1，R2，R3，R4，R5，R6，R7和R8如描述中所述，以及它们在各种前列腺素介导的疾病和障碍的治疗中作为前列腺素受体调节剂的用途，特别是作为前列腺素D2受体调节剂，以及包含这些化合物的制药组合物和它们的制备方法。
• Heterocyclyl Derivatives and their use as Prostaglandin D2 Receptor Modulators
  申请人：Actelion Pharmaceuticals Ltd.

  公开号：US20150252036A1

  公开（公告）日：2015-09-10

  The present invention relates to phenyl-substituted heterocyclyl derivatives of the formula (I), wherein Z, n, m, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and R 8 are as described in the description and their use as prostaglandin receptor modulators, most particularly as prostaglandin D 2 receptor modulators, in the treatment of various prostaglandin-mediated diseases and disorders, to pharmaceutical compositions containing these compounds and to processes for their preparation.

  本发明涉及公式（I）的苯基取代杂环基衍生物，其中Z，n，m，R1，R2，R3，R4，R5，R6，R7和R8如描述中所述，并且它们作为前列腺素受体调节剂的用途，特别是作为前列腺素D2受体调节剂，在治疗各种前列腺素介导的疾病和疾患中使用，以及包含这些化合物的制药组合物和它们的制备过程。
• Benzopyran derivatives and pharmaceutical compositions containing them
  申请人：Rhone-Poulenc Sante

  公开号：US04994470A1

  公开（公告）日：1991-02-19

  New benzopyran derivatives of general formula (I) in which: R.sub.1 denotes a hydrogen or halogen atom or a hydroxy, alkyloxy, nitro, amino, alkylsulphonamido, bis(alkylsulphonyl)amino, or acylamino radical, R denotes a radical of general formula: ##STR1## in which A denotes a single bond or a methylene radical and R.sub.2 and R.sub.3 which may be identical or different, denote a hydrogen or halogen atom or a hydroxy, alkyl, alkyloxy, nitro, amino, alkylsulphonamido, bis(alkylsulphonyl)amino, acylamino, sulphamoyl or cyano radical, or form together, when they are adjacent, a methylenedioxy or ethylenedioxy radical, or alternatively R denotes a 2-oxo-2H-benzimidazolyl radical, and R' and R" are identical and denote hydrogen atoms or alkyl radicals, their isomeric forms and their preparation. These new products are useful as antiarrhythmic and antifibrillating agents. ##STR2##

  通式（I）的新苯并吡喃衍生物中： R.sub.1代表氢原子或卤素原子或羟基，烷氧基，硝基，氨基，烷基磺酰胺基，双（烷基磺酰基）氨基或酰胺基基团， R代表一般式的基团：##STR1##其中A代表单键或亚甲基基团，R.sub.2和R.sub.3可以相同也可以不同，代表氢原子或卤素原子或羟基，烷基，烷氧基，硝基，氨基，烷基磺酰胺基，双（烷基磺酰基）氨基，酰胺基，磺酰基或氰基团，或者当它们相邻时，形成亚甲二氧基或乙二氧基基团，或者R代表2-氧代-2H-苯并咪唑基团，R'和R"相同，代表氢原子或烷基基团，它们的同分异构体及其制备方法。这些新产品可用作抗心律失常和抗心房颤动药物。##STR2##