methyl 6-ethyl-4-oxo-2-octynoate -Drug Synthesis Database

【结构式】

【分子编号】57432

【品名】methyl 6-ethyl-4-oxo-2-octynoate

【CA登记号】

【分子式】C₁₁H₁₆O₃

【分子量】196.24624

【元素组成】C 67.32% H 8.22% O 24.46%

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：(VIII)

The Wadsworth-Emmons condensation of 3-pentanone (I) with phosphonate (II) affords the conjugated ester adduct (III). Subsequent double bond hydrogenation in (III), in the presence of Pd/C, leads to the saturated ester (IV). After basic hydrolysis of the ethyl ester group of (IV), the resultant carboxylic acid (V) is activated as the corresponding acid chloride (VI) upon treatment with SOCl2. Then, acylation of the silver acetylide of methyl propiolate (VII) with acid chloride (VI) gives rise to the oxo ester intermediate (VIII).

参考文献中间体

合成目标

【1】 Mori, S.; Takechi, S.; Kida, S.; Mizui, T.; Ichihashi, T. (Shionogi & Co. Ltd.); Lignan analog, production thereof, and hypolipidemic drug. EP 0597107; EP 0701991; JP 1993310634; US 5731455; WO 9308155 .

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)	32415	Propione; Dimethylacetone; Diethyl ketone; 3-Pentanone	96-22-0	C₅H₁₀O	详情	详情
(II)	10019	Ethyl 2-(diethoxyphosphoryl)acetate; Triethyl phosphonoacetate	867-13-0	C₈H₁₇O₅P	详情	详情
(III)	57428	ethyl 3-ethyl-2-pentenoate		C₉H₁₆O₂	详情	详情
(IV)	57429	ethyl 3-ethylpentanoate		C₉H₁₈O₂	详情	详情
(V)	57433	3-ethylpentanoic acid		C₇H₁₄O₂	详情	详情
(VI)	57430	3-ethylpentanoyl chloride		C₇H₁₃ClO	详情	详情
(VII)	57431	(3-methoxy-3-oxo-1-propynyl)silver		C₄H₃AgO₂	详情	详情
(VIII)	57432	methyl 6-ethyl-4-oxo-2-octynoate		C₁₁H₁₆O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VIII)

Protection of 3,4,5-trimethoxybenzaldehyde (IX) with ethylene glycol (X) affords acetal (XI). After lithiation of (XI) by means of butyllithium, addition to veratraldehyde (XII) furnishes carbinol (XIII). Finally, cyclization of hydroxy acetal (XIII) with alkyne (VIII) under acidic conditions provides the title naphthol derivative.

参考文献中间体

合成目标

【1】 Mori, S.; Takechi, S.; Kida, S.; Mizui, T.; Ichihashi, T. (Shionogi & Co. Ltd.); Lignan analog, production thereof, and hypolipidemic drug. EP 0597107; EP 0701991; JP 1993310634; US 5731455; WO 9308155 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VIII)	57432	methyl 6-ethyl-4-oxo-2-octynoate		C₁₁H₁₆O₃	详情	详情
(IX)	11136	3,4,5-Trimethoxybenzaldehyde	86-81-7	C₁₀H₁₂O₄	详情	详情
(X)	11295	Polyethylene glycol;1,2-Ethanediol;Monoethylene glycol; Ethylene glycol	107-21-1	C₂H₆O₂	详情	详情
(XI)	57434	2-(3,4,5-trimethoxyphenyl)-1,3-dioxolane; 4-(1,3-dioxolan-2-yl)-2,6-dimethoxyphenyl methyl ether		C₁₂H₁₆O₅	详情	详情
(XII)	18304	3,4-Dimethoxybenzaldehyde; Veratraldehyde	120-14-9	C₉H₁₀O₃	详情	详情
(XIII)	57435	(3,4-dimethoxyphenyl)[6-(1,3-dioxolan-2-yl)-2,3,4-trimethoxyphenyl]methanol		C₂₁H₂₆O₈	详情	详情

合成路线3

该中间体在本合成路线中的序号：(X)

Addition of the lithium acetylide prepared from methyl propiolate (VIII) to 3-ethylpentanal (VII) gives methyl 6-ethyl-4-hydroxy-2-octynoate (IX), which is further oxidized to the corresponding keto ester (X) employing the Jones reagent in acetone. Cycloaddition between alkyne (X) and the lithium derivative of the isobenzofuranone (V) gives rise to the 1,4-epoxy dihydronaphthalene adduct (XI). Subsequent acidic hydrolysis of (XI) furnishes the hydroxy naphthalenone (XII). Finally, reductive aromatization of (XII) using TiCl3 produces the title naphthol compound.

参考文献中间体

合成目标

【1】 Mori, S.; Takechi, S.; Kida, S. (Shionogi & Co. Ltd.); Process for producing lignan cpd.. EP 0646570; WO 9424087 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VII)	57444	3-ethylpentanal		C₇H₁₄O	详情	详情
(VIII)	19588	methyl propiolate	922-67-8	C₄H₄O₂	详情	详情
(IX)	57445	methyl 6-ethyl-4-hydroxy-2-octynoate		C₁₁H₁₈O₃	详情	详情
(X)	57432	methyl 6-ethyl-4-oxo-2-octynoate		C₁₁H₁₆O₃	详情	详情
(XI)	57443	3-(3,4-dimethoxyphenyl)-4,5,6-trimethoxy-2-benzofuran-1(3H)-one		C₁₉H₂₀O₇	详情	详情
(XII)	57446	methyl 8-(3,4-dimethoxyphenyl)-10-(3-ethylpentanoyl)-4,5,6-trimethoxy-1-[(trimethylsilyl)oxy]-11-oxatricyclo[6.2.1.0~2,7~]undeca-2,4,6,9-tetraene-9-carboxylate		C₃₃H₄₄O₁₀Si	详情	详情

Extended Information