5,7-dimethoxy-4-methyl-2-benzofuran-1(3H)-one -Drug Synthesis Database

【结构式】

【分子编号】39954

【品名】5,7-dimethoxy-4-methyl-2-benzofuran-1(3H)-one

【CA登记号】

【分子式】C₁₁H₁₂O₄

【分子量】208.21388

【元素组成】C 63.45% H 5.81% O 30.74%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(XXVI)

The condensation of diethyl malonate (XV) with 3-methylpent-3-en-2-one (XVI) by means of sodium ethoxide in ethanol gives 5,6-dimethyl-4-ethoxycarbonylcyclohexane-1,3-dione (XVII), which is aromatized to 5,6-dimethyl-4-ethoxycarbonylresorcinol (XIX) by treatment with FeCl3 in refluxing acetic acid, or by bromination to 2-bromo-5,6-dimethyl-4-ethoxycarbonylresorcinol and debromination with H2 over Pd/C. The methylation of (XIX) with diazomethane or methyl iodide and K2CO3 gives the corresponding dimethyl ether (XX), which is hydrolyzed with NaOH affording 2,4-dimethoxy-5,6-dimethylbenzoic acid (XXI). This acid by reaction with SOCl2 gives the acyl chloride (XXII), which by reaction with NH3 is converted into the amide (XXIII). The reaction of (XXIII) with tert-butyl hypochlorite affords the N-chloroamide (XXIV), which is photolyzed to the intermediate iminolactone (XXV) and immediately hydrolyzed to 4-methyl-5,7-dimethoxyphthalide (XXVI).

参考文献中间体

合成目标

【1】 Canonica, L.; et al.; Total synthesis of mycophenolic acid. Tetrahedron Lett 1971, 28, 2691-92.
【2】 Castaner, J.; Hillier, K.; Mycophenolic acid. Drugs Fut 1978, 3, 8, 594.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XV)	16825	2-[4-(tert-butoxy)-5-fluoro-3-methyl-2-pyridinyl]-2-cyclopropylacetonitrile		C₁₅H₁₉FN₂O	详情	详情
(XVI)	39944	(E)-3-methyl-3-penten-2-one	565-62-8	C₆H₁₀O	详情	详情
(XVII)	39945	ethyl 2,3-dimethyl-4,6-dioxocyclohexanecarboxylate		C₁₁H₁₆O₄	详情	详情
(XVIII)	39946	ethyl 3-bromo-2,4-dihydroxy-5,6-dimethylbenzoate		C₁₁H₁₃BrO₄	详情	详情
(XIX)	39947	ethyl 4,6-dihydroxy-2,3-dimethylbenzoate		C₁₁H₁₄O₄	详情	详情
(XX)	39948	ethyl 4,6-dimethoxy-2,3-dimethylbenzoate		C₁₃H₁₈O₄	详情	详情
(XXI)	39949	4,6-dimethoxy-2,3-dimethylbenzoic acid		C₁₁H₁₄O₄	详情	详情
(XXII)	39950	4,6-dimethoxy-2,3-dimethylbenzoyl chloride		C₁₁H₁₃ClO₃	详情	详情
(XXIII)	39951	4,6-dimethoxy-2,3-dimethylbenzamide		C₁₁H₁₅NO₃	详情	详情
(XXIV)	39952	N-chloro-4,6-dimethoxy-2,3-dimethylbenzamide		C₁₁H₁₄ClNO₃	详情	详情
(XXV)	39953	5,7-dimethoxy-4-methyl-2-benzofuran-1(3H)-imine		C₁₁H₁₃NO₃	详情	详情
(XXVI)	39954	5,7-dimethoxy-4-methyl-2-benzofuran-1(3H)-one		C₁₁H₁₂O₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XXVI)

The reaction of (XXVI) with HI and red P in acetic acid gives 4-methyl-5,7-dihydroxyphthalide (XXVII), which is condensed with methyl 6-bromo-4-methyl-4-hexenoate (XXVIII) by means of Ag2O in dioxane yielding the methyl ester (XXIX). The monomethylation of (XXIX) with diazomethane in benzene affords the methyl ester of mycophenolic acid (XXX), which is finally hydrolyzed with aqueous NaOH.

参考文献中间体

合成目标

【1】 Castaner, J.; Hillier, K.; Mycophenolic acid. Drugs Fut 1978, 3, 8, 594.
【2】 Canonica, L.; et al.; Total synthesis of mycophenolic acid. Tetrahedron Lett 1971, 28, 2691-92.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XXVI)	39954	5,7-dimethoxy-4-methyl-2-benzofuran-1(3H)-one	C₁₁H₁₂O₄	详情	详情
(XXVII)	39955	5,7-dihydroxy-4-methyl-2-benzofuran-1(3H)-one	C₉H₈O₄	详情	详情
(XXVIII)	39956	methyl (E)-6-bromo-4-methyl-4-hexenoate	C₈H₁₃BrO₂	详情	详情
(XXIX)	39957	methyl (E)-6-(4,6-dihydroxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methyl-4-hexenoate	C₁₇H₂₀O₆	详情	详情
(XXX)	39958	methyl (E)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-2-benzofuran-5-yl)-4-methyl-4-hexenoate	C₁₈H₂₂O₆	详情	详情

Extended Information