methyl 5-formyl-2-hydroxybenzoate -Drug Synthesis Database

【结构式】

【分子编号】32356

【品名】methyl 5-formyl-2-hydroxybenzoate

【CA登记号】

【分子式】C₉H₈O₄

【分子量】180.16012

【元素组成】C 60% H 4.48% O 35.52%

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：(VI)

The formylation of 1,4-dimethoxybenzene (I) with C6H11-Li, TMEDA and DMF gives 2,5-dimethoxybenzaldehyde (II), which is reduced with NaBH4 to the corresponding alcohol (III). The treatment of (III) with HBr affords the benzyl bromide (IV), which by reaction with PPh3 in hot toluene is converted into the phosphonium salt (V). The condensation of (V) with 5-formyl-2-hydroxybenzoic acid methyl ester (VI)(obtained by esterification of the corresponding acid (VII) with methanol and H2SO4) by means of LDA in THF affords the stilbene (VIII). Finally, this compound is reduced with H2 over Pd/C in ethyl acetate.

参考文献中间体

合成目标

【1】 Kucerovy, A.; et al.; An efficient large-scale synthesis of methyl 5-[2-82,5-dimethoxyphenyl)ethyl]-2-hydroxybenzoate. Org Process Res Dev 1997, 1, 4, 287.

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)	21946	1,4-dimethoxybenzene; 4-methoxyphenyl methyl ether	150-78-7	C₈H₁₀O₂	详情	详情
(II)	10174	2,5-Dimethoxybenzaldehyde	93-02-7	C₉H₁₀O₃	详情	详情
(III)	32353	(2,5-dimethoxyphenyl)methanol	33524-31-1	C₉H₁₂O₃	详情	详情
(IV)	32354	2-(bromomethyl)-4-methoxyphenyl methyl ether; 2-(bromomethyl)-1,4-dimethoxybenzene		C₉H₁₁BrO₂	详情	详情
(V)	32355	(2,5-dimethoxybenzyl)(triphenyl)phosphonium bromide		C₂₇H₂₆BrO₂P	详情	详情
(VI)	32356	methyl 5-formyl-2-hydroxybenzoate		C₉H₈O₄	详情	详情
(VII)	32357	5-Formylsalicylic acid; 5-formyl-2-hydroxybenzoic acid	616-76-2	C₈H₆O₄	详情	详情
(VIII)	32358	methyl 5-[(E)-2-(2,5-dimethoxyphenyl)ethenyl]-2-hydroxybenzoate		C₁₈H₁₈O₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

Improved large scale synthesis: The formylation of 1,4-dimethoxybenzene (I) with C6H11-Li, TMEDA and DMF gives 2,5-dimethoxybenzaldehyde (II), which is reduced with NaBH4 in toluene/methanol to the corresponding alcohol (III). The treatment of (III) with PBr3 in ethyl acetate affords the benzyl bromide (IV), which by reaction with dimethyl phosphite (IX) and NaH in toluene is converted into the phosphonate (X). The condensation of (X) with 5-formyl-2-hydroxybenzoic acid methyl ester (VI)(obtained by esterification of the corresponding acid (VII) with methanol and H2SO4) by means of LiHMDS in THF affords the stilbene (VIII). Finally, this compound is reduced with H2 over Pd/C in ethyl acetate.

参考文献中间体

合成目标

【1】 Kucerovy, A.; et al.; An efficient large-scale synthesis of methyl 5-[2-82,5-dimethoxyphenyl)ethyl]-2-hydroxybenzoate. Org Process Res Dev 1997, 1, 4, 287.

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)	21946	1,4-dimethoxybenzene; 4-methoxyphenyl methyl ether	150-78-7	C₈H₁₀O₂	详情	详情
(II)	10174	2,5-Dimethoxybenzaldehyde	93-02-7	C₉H₁₀O₃	详情	详情
(III)	32353	(2,5-dimethoxyphenyl)methanol	33524-31-1	C₉H₁₂O₃	详情	详情
(IV)	32354	2-(bromomethyl)-4-methoxyphenyl methyl ether; 2-(bromomethyl)-1,4-dimethoxybenzene		C₉H₁₁BrO₂	详情	详情
(VI)	32356	methyl 5-formyl-2-hydroxybenzoate		C₉H₈O₄	详情	详情
(VII)	32357	5-Formylsalicylic acid; 5-formyl-2-hydroxybenzoic acid	616-76-2	C₈H₆O₄	详情	详情
(VIII)	32358	methyl 5-[(E)-2-(2,5-dimethoxyphenyl)ethenyl]-2-hydroxybenzoate		C₁₈H₁₈O₅	详情	详情
(IX)	32359	dimethyl phosphonate	868-85-9	C₂H₇O₃P	详情	详情
(X)	32360	dimethyl 2,5-dimethoxybenzylphosphonate		C₁₁H₁₇O₅P	详情	详情

Extended Information