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Aceclofenac, YT-919, Beofenac, Preservex, Gerbin, Falcon, Airtal

醋氯芬酸Chemical Name: Glycolic acid [2-(2,6-dichloroanilino)phenyl]acetate ester; 2-(2,6-Dichlorophenylamino)phenylacetic acid carboxymethyl ester; 2-[2-(2,6-Dichlorophenylamino)phenylacetoxy]acetic acid
CAS No. 89796-99-6
项目整合开发状态: Launched-1992
项目研究机构: Almirall Prodesfarma (Originator), Bristol-Myers Squibb (Licensee), Daewoong (Licensee), Gedeon Richter (Licensee), UCB (Licensee), Yakult Honsha (Licensee)
合成路线:Alkylation of the sodium salt of diclofenac (I) with benzyl bromoacetate (II) in hot DMF yielded the (arylacetoxy)acetate (III).Subsequent hydrogenolysis of the benzyl ester of (III) in the presence of Pd/C gave the title carboxylic acid.Alternatively,the benzyl ester group of (III) was cleaved by means of the combination of chlorotrimethylsilane and sodium iodide.This method of selective ester hydrolysis with in situ generated iodotrimethylsilane was also applied to the corresponding methyl (IV) and tert-butyl (V) esters.In a related procedure,tert-butyl ester (V) was prepared by alkylation of diclofenac (VI) with tert-butyl bromoacetate (VII) in the presence of tertiary amines.Selective cleavage of the tert-butyl ester group of (V) was then performed by treatment with either trifluoroacetic or formic acid.
📌 参考资料/链接:
参考文献标题:2-[(2,6-Dichlorophenyl)amino]phenylacetoxyacetyl derivs.and therapeutic compsns.containing same
文献作者:Casas,A.V.(Almirall Prodesfarma,SA)
参考来源:EP 0119932; US 4548952

📄 详细内容


合成路线:Alkylation of the sodium salt of diclofenac (I) with benzyl bromoacetate (II) in hot DMF yielded the (arylacetoxy)acetate (III).Subsequent hydrogenolysis of the benzyl ester of (III) in the presence of Pd/C gave the title carboxylic acid.Alternatively,the benzyl ester group of (III) was cleaved by means of the combination of chlorotrimethylsilane and sodium iodide.This method of selective ester hydrolysis with in situ generated iodotrimethylsilane was also applied to the corresponding methyl (IV) and tert-butyl (V) esters.In a related procedure,tert-butyl ester (V) was prepared by alkylation of diclofenac (VI) with tert-butyl bromoacetate (VII) in the presence of tertiary amines.Selective cleavage of the tert-butyl ester group of (V) was then performed by treatment with either trifluoroacetic or formic acid.

参考文献标题:Process for obtaining 2-[(2,6-dichlorophenyl)amino]phenylacetoxyacetic acid
文献作者:Ginebreda Mart? A.; Agust?Cruz,A.(Almirall Prodesfarma,SA)
参考来源:ES 2020146


合成路线:Alkylation of the sodium salt of diclofenac (I) with benzyl bromoacetate (II) in hot DMF yielded the (arylacetoxy)acetate (III).Subsequent hydrogenolysis of the benzyl ester of (III) in the presence of Pd/C gave the title carboxylic acid.Alternatively,the benzyl ester group of (III) was cleaved by means of the combination of chlorotrimethylsilane and sodium iodide.This method of selective ester hydrolysis with in situ generated iodotrimethylsilane was also applied to the corresponding methyl (IV) and tert-butyl (V) esters.In a related procedure,tert-butyl ester (V) was prepared by alkylation of diclofenac (VI) with tert-butyl bromoacetate (VII) in the presence of tertiary amines.Selective cleavage of the tert-butyl ester group of (V) was then performed by treatment with either trifluoroacetic or formic acid.

参考文献标题:Process for the preparation of aceclofenac
文献作者:Schickaneder,H.; Nikolopoulos,A.; Murphy,T.
参考来源:WO 9955660


合成路线:Aceclofenac was prepared by selective hydrolysis of other labile ester precursors.Alkylation of diclofenac sodium (I) with tetrahydropyranyl chloroacetate (IX),prepared by protection of chloroacetic acid (VIII) with dihydropyran,furnished the tetrahydropyranyl ester of aceclofenac (X),which was then deprotected by treatment with HCl.Similarly,the preparation of aceclofenac was reported by acidic hydrolysis of the analogous tetrahydrofuranyl ester (XI).

参考文献标题:Process for obtaining 2-[(2,6-dichlorophenyl)amino]phenylacetoxy acetic acid
文献作者:Flores Ramos,R.(Almirall Prodesfarma,SA)
参考来源:ES 2046141


合成路线:Aceclofenac was prepared by selective hydrolysis of other labile ester precursors.Alkylation of diclofenac sodium (I) with tetrahydropyranyl chloroacetate (IX),prepared by protection of chloroacetic acid (VIII) with dihydropyran,furnished the tetrahydropyranyl ester of aceclofenac (X),which was then deprotected by treatment with HCl.Similarly,the preparation of aceclofenac was reported by acidic hydrolysis of the analogous tetrahydrofuranyl ester (XI).
参考文献标题:Process for the preparation of a phenylacetic acid deriv.
文献作者:Zirngibl,L.; Gnehm,R.(Siegfried AG)
参考来源:CH 682747


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