Isoprofen, UP-517-03

异洛芬Chemical Name: 2-(2-Isopropylindan-5-yl)propionic acid
CAS No. 57144-56-6, 58453-65-9 (sodium salt)
项目整合开发状态: Biological Testing
项目研究机构:
合成路线:The Friedel-Kraft抯 reaction of 2-isopropylindan (I) with ethyloxalyl chloride (II) by means of AlCl3 in methylene chloride gives ethyl 2-(2-isopropyl-5-indanyl)-2-oxoacetate (III),which is hydrolyzed with NaOH in refluxing ethanol to the corresponding free acid (IV).The reaction of (IV) with methylmagnesium iodide in ether yields 2-(2-isopropyl-5-indanyl)-2-hydroxypropionic acid (V),which is dehydrated with H2SO4 in refluxing dioxane affording 2-(2-isopropyl-5-indanyl)acrylic acid (VI) (1,2,4).Finally this compound is reduced with H2 over Raney-Ni or Pd/C in methanol or dioxane

合成路线:The Friedel-Kraft抯 reaction of 2-isopropylindan (I) with acetic anhydride in methylene chloride gives 2-isopropyl-5-acetylindan (VII),which by with sulfur and morpholine (A) at 140 C gives 2-(2-isopropyl-5-indanyl)acetylmorpholinothioamide (XI),which is hydrolyzed to 2-(2-isopropyl-5-indanyl)acetic acid (XII).The esterification of (XII) with ethanol - H2SO4 yields the corresponding ethyl ester (XIII),which is condensed with diethyl carbonate (XIV) by means of sodium ethoxide in refluxing ethanol affording diethyl (2-isopropyl-5-indanyl)malonate (XV),which is methylated with methyl iodide and sodium ethoxide in refluxing ethanol to give diethyl methyl-(2-isopropyl-5-indanyl)malonate (XVI).Finally this compound is hydrolyzed and decarboxylated by treatment with NaOH in refluxing hydrazine hydrateCompound (XII) can also be obtained by a Wolf-Kistner reduction of ketoacid (IV) in refluxing hydrazine hydrate

合成路线:The Friedel-Kraft抯 reaction of 2-isopropylindan (I) with acetic anhydride in methylene chloride gives 2-isopropyl-5-acetylindan (VII),which is reduced with KBH4 in methanol yielding 2-isopropyl-5-(1-hydroxyethyl)indan (VIII).The treatment of (VIII) with SOCl2 in benzene affords 2-isopropyl-5-(1-chloroethyl)indan (IX),which by reaction with NaCN in hot HMPA yields 2-(2-isopropyl-5-indanyl)propionitrile (X).Finally this compound is hydrolyzed with H2SO4 in refluxing acetic acid - water
📌 参考资料/链接:
参考文献标题:Isoprofen
文献作者:Blancafort,P.; Serradell,M.N.; Castar,J.; Arrigoni,Martelli,E.
参考来源:Drugs Fut 1981,6(8),471

📄 详细内容


合成路线:The Friedel-Kraft抯 reaction of 2-isopropylindan (I) with ethyloxalyl chloride (II) by means of AlCl3 in methylene chloride gives ethyl 2-(2-isopropyl-5-indanyl)-2-oxoacetate (III),which is hydrolyzed with NaOH in refluxing ethanol to the corresponding free acid (IV).The reaction of (IV) with methylmagnesium iodide in ether yields 2-(2-isopropyl-5-indanyl)-2-hydroxypropionic acid (V),which is dehydrated with H2SO4 in refluxing dioxane affording 2-(2-isopropyl-5-indanyl)acrylic acid (VI) (1,2,4).Finally this compound is reduced with H2 over Raney-Ni or Pd/C in methanol or dioxane

合成路线:The Friedel-Kraft抯 reaction of 2-isopropylindan (I) with acetic anhydride in methylene chloride gives 2-isopropyl-5-acetylindan (VII),which is reduced with KBH4 in methanol yielding 2-isopropyl-5-(1-hydroxyethyl)indan (VIII).The treatment of (VIII) with SOCl2 in benzene affords 2-isopropyl-5-(1-chloroethyl)indan (IX),which by reaction with NaCN in hot HMPA yields 2-(2-isopropyl-5-indanyl)propionitrile (X).Finally this compound is hydrolyzed with H2SO4 in refluxing acetic acid - water

参考文献标题:Antiinflammatory and analgesic diastereoisomeric derivatives of indan-5-acetic acid
文献作者:Teulon,J.M.; et al.
参考来源:J Med Chem 1978,21(4),901


合成路线:The Friedel-Kraft抯 reaction of 2-isopropylindan (I) with ethyloxalyl chloride (II) by means of AlCl3 in methylene chloride gives ethyl 2-(2-isopropyl-5-indanyl)-2-oxoacetate (III),which is hydrolyzed with NaOH in refluxing ethanol to the corresponding free acid (IV).The reaction of (IV) with methylmagnesium iodide in ether yields 2-(2-isopropyl-5-indanyl)-2-hydroxypropionic acid (V),which is dehydrated with H2SO4 in refluxing dioxane affording 2-(2-isopropyl-5-indanyl)acrylic acid (VI) (1,2,4).Finally this compound is reduced with H2 over Raney-Ni or Pd/C in methanol or dioxane

合成路线:The Friedel-Kraft抯 reaction of 2-isopropylindan (I) with acetic anhydride in methylene chloride gives 2-isopropyl-5-acetylindan (VII),which by with sulfur and morpholine (A) at 140 C gives 2-(2-isopropyl-5-indanyl)acetylmorpholinothioamide (XI),which is hydrolyzed to 2-(2-isopropyl-5-indanyl)acetic acid (XII).The esterification of (XII) with ethanol - H2SO4 yields the corresponding ethyl ester (XIII),which is condensed with diethyl carbonate (XIV) by means of sodium ethoxide in refluxing ethanol affording diethyl (2-isopropyl-5-indanyl)malonate (XV),which is methylated with methyl iodide and sodium ethoxide in refluxing ethanol to give diethyl methyl-(2-isopropyl-5-indanyl)malonate (XVI).Finally this compound is hydrolyzed and decarboxylated by treatment with NaOH in refluxing hydrazine hydrateCompound (XII) can also be obtained by a Wolf-Kistner reduction of ketoacid (IV) in refluxing hydrazine hydrate

合成路线:The Friedel-Kraft抯 reaction of 2-isopropylindan (I) with acetic anhydride in methylene chloride gives 2-isopropyl-5-acetylindan (VII),which is reduced with KBH4 in methanol yielding 2-isopropyl-5-(1-hydroxyethyl)indan (VIII).The treatment of (VIII) with SOCl2 in benzene affords 2-isopropyl-5-(1-chloroethyl)indan (IX),which by reaction with NaCN in hot HMPA yields 2-(2-isopropyl-5-indanyl)propionitrile (X).Finally this compound is hydrolyzed with H2SO4 in refluxing acetic acid - water

参考文献标题:
文献作者:Teulon,J.M.; et al.(Hexachimie SA)
参考来源:BE 824522; CA 1063618; CH 603533; CH 605567; DD 117209; DD 118271; DD 123319; DE 2504689; FR 2260334; GB 1492175; JP 76125367; JP 76125368; NL 7501518; NL 7501519; US 4069326; US 4088787; US 4182896; ZA 7500707


合成路线:The Friedel-Kraft抯 reaction of 2-isopropylindan (I) with ethyloxalyl chloride (II) by means of AlCl3 in methylene chloride gives ethyl 2-(2-isopropyl-5-indanyl)-2-oxoacetate (III),which is hydrolyzed with NaOH in refluxing ethanol to the corresponding free acid (IV).The reaction of (IV) with methylmagnesium iodide in ether yields 2-(2-isopropyl-5-indanyl)-2-hydroxypropionic acid (V),which is dehydrated with H2SO4 in refluxing dioxane affording 2-(2-isopropyl-5-indanyl)acrylic acid (VI) (1,2,4).Finally this compound is reduced with H2 over Raney-Ni or Pd/C in methanol or dioxane

参考文献标题:
文献作者:Payne,T.G.(Hexachimie SA)
参考来源:CH 605565


合成路线:The Friedel-Kraft抯 reaction of 2-isopropylindan (I) with ethyloxalyl chloride (II) by means of AlCl3 in methylene chloride gives ethyl 2-(2-isopropyl-5-indanyl)-2-oxoacetate (III),which is hydrolyzed with NaOH in refluxing ethanol to the corresponding free acid (IV).The reaction of (IV) with methylmagnesium iodide in ether yields 2-(2-isopropyl-5-indanyl)-2-hydroxypropionic acid (V),which is dehydrated with H2SO4 in refluxing dioxane affording 2-(2-isopropyl-5-indanyl)acrylic acid (VI) (1,2,4).Finally this compound is reduced with H2 over Raney-Ni or Pd/C in methanol or dioxane
参考文献标题:
文献作者:Payne,T.G.(Hexachimie SA)
参考来源:CH 605564


产品链接: CAS No. 57144-56-6››