sodium 2-[2-(2,6-dichloroanilino)phenyl]acetate -Drug Synthesis Database

【结构式】

【分子编号】56535

【品名】sodium 2-[2-(2,6-dichloroanilino)phenyl]acetate

【CA登记号】

【分子式】C₁₄H₁₀Cl₂NNaO₂

【分子量】318.134108

【元素组成】C 52.86% H 3.17% Cl 22.29% N 4.4% Na 7.23% O 10.06%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(I)

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.

参考文献中间体

合成目标

【1】 Casas, A.V. (Almirall Prodesfarma, SA); 2-[(2,6-Dichlorophenyl)amino]phenylacetoxyacetyl derivs. and therapeutic compsns. containing same. EP 0119932; US 4548952 .
【2】 Ginebreda Martí, A.; Agustí Cruz, A. (Almirall Prodesfarma, SA); Process for obtaining 2-[(2,6-dichlorophenyl)amino]phenylacetoxyacetic acid. ES 2020146 .
【3】 Schickaneder, H.; Nikolopoulos, A.; Murphy, T.; Process for the preparation of aceclofenac. WO 9955660 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	56535	sodium 2-[2-(2,6-dichloroanilino)phenyl]acetate		C₁₄H₁₀Cl₂NNaO₂	详情	详情
(II)	12869	benzyl 2-bromoacetate	5437-45-6	C₉H₉BrO₂	详情	详情
(III)	56536	2-(benzyloxy)-2-oxoethyl 2-[2-(2,6-dichloroanilino)phenyl]acetate		C₂₃H₁₉Cl₂NO₄	详情	详情
(IV)	56537	2-methoxy-2-oxoethyl 2-[2-(2,6-dichloroanilino)phenyl]acetate		C₁₇H₁₅Cl₂NO₄	详情	详情
(V)	56538	2-(tert-butoxy)-2-oxoethyl 2-[2-(2,6-dichloroanilino)phenyl]acetate		C₂₀H₂₁Cl₂NO₄	详情	详情
(VI)	33701	Diclofenac; 2-[2-(2,6-Dichloroanilino)phenyl]acetic acid		C₁₄H₁₁Cl₂NO₂	详情	详情
(VII)	17430	2-Bromoacetic acid tert-butyl ester; tert-butyl 2-bromoacetate; tert-Butyl bromoacetate	5292-43-3	C₆H₁₁BrO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

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).

参考文献中间体

合成目标

【1】 Flores Ramos, R. (Almirall Prodesfarma, SA); Process for obtaining 2-[(2,6-dichlorophenyl)amino]phenylacetoxy acetic acid. ES 2046141 .
【2】 Zirngibl, L.; Gnehm, R. (Siegfried AG); Process for the preparation of a phenylacetic acid deriv.. CH 682747 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	56535	sodium 2-[2-(2,6-dichloroanilino)phenyl]acetate		C₁₄H₁₀Cl₂NNaO₂	详情	详情
(VIII)	11847	2-Chloroacetic acid; Chloroacetic Acid	79-11-8	C₂H₃ClO₂	详情	详情
(IX)	56539	tetrahydro-2H-pyran-2-yl 2-chloroacetate		C₇H₁₁ClO₃	详情	详情
(X)	56540	2-oxo-2-(tetrahydro-2H-pyran-2-yloxy)ethyl 2-[2-(2,6-dichloroanilino)phenyl]acetate		C₂₁H₂₁Cl₂NO₅	详情	详情
(XI)	56541	2-oxo-2-(tetrahydro-2-furanyloxy)ethyl 2-[2-(2,6-dichloroanilino)phenyl]acetate		C₂₀H₁₉Cl₂NO₅	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

Alternatively, alkylation of diclofenac sodium (I) with either trichloroethyl bromoacetate (XII) of tribromoethyl bromoacetate (XIII) gave rise to the respective trichloroethyl (XIV) and tribromoethyl (XV) esters of aceclofenac. Reductive cleavage of the trihaloethyl esters (XIV) and (XV) using zinc powder under acidic conditions furnished the title compound.

参考文献中间体

合成目标

【1】 Frank, A.; Karn, H.; Spanig, H. (Abbott GmbH & Co. KG); Production of 1-hydroxyalkyl-5-nitroimidazoles. DE 2359625; FR 2253019; GB 1481349 .
【2】 Frank, A.; Dockner, T.; Karn, H. (Abbott GmbH & Co. KG); Process for the preparation of 1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole of high purity. EP 0150407 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	56535	sodium 2-[2-(2,6-dichloroanilino)phenyl]acetate	C₁₄H₁₀Cl₂NNaO₂	详情	详情
(XII)	56542	2,2,2-trichloroethyl 2-bromoacetate	C₄H₄BrCl₃O₂	详情	详情
(XIII)	56543	2,2,2-tribromoethyl 2-bromoacetate	C₄H₄Br₄O₂	详情	详情
(XIV)	56544	2-oxo-2-(2,2,2-trichloroethoxy)ethyl 2-[2-(2,6-dichloroanilino)phenyl]acetate	C₁₈H₁₄Cl₅NO₄	详情	详情
(XV)	56545	2-oxo-2-(2,2,2-tribromoethoxy)ethyl 2-[2-(2,6-dichloroanilino)phenyl]acetate	C₁₈H₁₄Br₃Cl₂NO₄	详情	详情

Extended Information