2-(3,4-Dichloro-phenyl)-4-phenyl-butyric acid | 4800-45-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: 2-(3,4-Dichloro-phenyl)-4-phenyl-butyric acid
• 英文别名: 2-(3,4-Dichlorophenyl)-4-phenylbutanoic acid
• CAS: 4800-45-7
• 化学式: C₁₆H₁₄Cl₂O₂
• 分子量: 309.192
• InChiKey: LADHGNMGGWVUQO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

文献信息

• Process for preparing a 4,4-diphenylbutanoic acid derivative
  申请人：PFIZER INC.

  公开号：EP0295050A1

  公开（公告）日：1988-12-14

  A novel three-step process for preparing 4-(3,4-­dichlorophenyl)-4-phenylbutanoic acid is disclosed, which involves (1) reducing 4-(3,4-dichlorophenyl)-­4-ketobutanoic acid to 4-(3,4-dichlorophenyl)-4-­hydroxybutanoic acid; (2) then converting the inter­mediate hydroxy acid formed in the first step to 5-(3,4-dichlorophenyl)-dihydro-2(3H)-furanone, and (3) thereafter reacting the resulting gamma-butyrolactone compound with benzene in a Friedel-Crafts type reaction to form the desired final product. The latter compound is known to be useful as an intermediate leading to 4-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenone and ultimately, to cis-(1S)(4S)-N-methyl-4-(3,4-­dichlorophenyl)-1,2,3,4-tetrahydro-1-naphthaleneamine (sertraline), which is known to be a preferred anti-depressant agent in the field of medicinal chemistry. The aforementioned 5-(3,4-dichloro­phenyl)-dihydro-2(3H)-furanone and 4-(3,4-dichloro­phenyl)-4-hydroxybutanoic acid are both novel compounds. There is also disclosed a novel process for converting 5-(3,4-dichlorophenyl)-dihydro-2(3H)-­furanone directly to 4-(3,4-dichlorophenyl)-3,4-­dihydro-1(2H)-naphthalenone, as well as an alternate novel process for converting 4-(3,4-dichlorophenyl)-4-­hydroxybutanoic acid directly to this same key intermediate.

  本发明公开了一种分三步制备 4-(3,4-二氯苯基)-4-苯基丁酸的新工艺，包括 (1) 将 4-(3,4-二氯苯基)-4-酮丁酸还原为 4-(3,4-二氯苯基)-4-羟基丁酸；(2) 然后将第一步中生成的中间羟基酸转化为 5-(3,4-二氯苯基)-二氢-2(3H)-呋喃酮，以及 (3) 之后将生成的γ-丁内酯化合物与苯进行弗里德尔-卡夫斯反应，生成所需的最终产品。众所周知，后一种化合物可以作为中间体，进而生成 4-(3,4-二氯苯基)-3,4-二氢-1(2H)-萘酮，并最终生成顺式-(1S)(4S)-N-甲基-4-(3,4-二氯苯基)-1,2,3,4-四氢-1-萘胺（舍曲林），而舍曲林是药物化学领域的首选抗抑郁剂。上述 5-(3,4-二氯苯基)-二氢-2(3H)-呋喃酮和 4-(3,4-二氯苯基)-4-羟基丁酸都是新型化合物。此外，还公开了一种将 5-(3,4-二氯苯基)-二氢-2(3H)-呋喃酮直接转化为 4-(3,4-二氯苯基)-3,4-二氢-1(2H)-萘酮的新型工艺，以及另一种将 4-(3,4-二氯苯基)-4-羟基丁酸直接转化为该关键中间体的新型工艺。