4-[4-(methoxymethoxy)phenyl]butanoic acid -Drug Synthesis Database

【结构式】

【分子编号】55601

【品名】4-[4-(methoxymethoxy)phenyl]butanoic acid

【CA登记号】

【分子式】C₁₂H₁₆O₄

【分子量】224.25664

【元素组成】C 64.27% H 7.19% O 28.54%

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：(XIII)

The intermediate carboxylic acid (XIII) was prepared as follows: 2-(4-Hydroxyphenyl)ethanol (VI) was selectively protected at the phenolic hydroxyl with benzyl bromide, yielding (VII). Subsequent oxidation of the aliphatic alcohol group of (VII) with Dess-Martin periodinane reagent provided aldehyde (VIII). Wadsworth-Emmons condensation of (VIII) with the sodium derivative of phosphonate (IX) furnished adduct (X), which was further hydrogenated over Pd/C to the saturated ester (XI). The phenolic hydroxyl group of (XI), which was concomitantly debenzylated in the preceding hydrogenation step, was further reprotected as the methoxymethyl ether (XII). Acid (XIII) was then obtained by basic hydrolysis of ester (XII).

参考文献中间体

合成目标

【1】 Takaoka, E.; et al.; Catalytic asymmetric synthesis of arbutamine. Heterocycles 1997, 46, 157.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VI)	47355	4-(2-hydroxyethyl)phenol	501-94-0	C₈H₁₀O₂	详情	详情
(VII)	33328	2-(p-Benzyloxyphenyl)ethanol; 2-[4-(Benzyloxy)phenyl]-1-ethanol		C₁₅H₁₆O₂	详情	详情
(VIII)	55597	2-[4-(benzyloxy)phenyl]acetaldehyde		C₁₅H₁₄O₂	详情	详情
(IX)	10019	Ethyl 2-(diethoxyphosphoryl)acetate; Triethyl phosphonoacetate	867-13-0	C₈H₁₇O₅P	详情	详情
(X)	55598	ethyl (E)-4-[4-(benzyloxy)phenyl]-2-butenoate		C₁₉H₂₀O₃	详情	详情
(XI)	55599	ethyl 4-(4-hydroxyphenyl)butanoate		C₁₂H₁₆O₃	详情	详情
(XII)	55600	ethyl 4-[4-(methoxymethoxy)phenyl]butanoate		C₁₄H₂₀O₄	详情	详情
(XIII)	55601	4-[4-(methoxymethoxy)phenyl]butanoic acid		C₁₂H₁₆O₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XIII)

Protection of 3,4-dihydroxybenzaldehyde (XVI) with t-butyldimethylsilyl chloride and imidazole provided the corresponding bis-silyl ether (XVII) (2). Asymmetric nitroaldol condensation of aldehyde (XVII) with nitromethane in the presence of the chiral samarium tris(binaphthoxide) complex (XV) --prepared from (S)-6,6'-bis(trimethylsilylethynyl)-1,1'-dihydroxy-2,2'-binaphthalene (XIV) and samarium triisopropoxide in the presence of BuLi (2,3)-- gave rise to the (R)-nitro alcohol adduct (XVIII) with high optical purity. Catalytic hydrogenation of the nitro group of (XVIII) furnished the silylated norepinephrine (XIX), which was coupled with acid (XIII) in the presence of diethylphosphoryl cyanide to yield amide (XX). Reduction of amide (XX) with LiAlH4 gave amine (XXI). The silyl and methoxymethyl protecting groups were finally removed under acidic conditions to furnish the title compound.

参考文献中间体

合成目标

【1】 Takaoka, E.; et al.; Catalytic asymmetric synthesis of arbutamine. Heterocycles 1997, 46, 157.
【2】 Shibasaki, M.; Fujita, M.; Urata, Y.; Sasai, H. (Chisso Corp.); Optically active nitro alcohol derivs., optically active amino alcohol derivates, and process for preparing the same. EP 0947498; WO 9824753 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XIII)	55601	4-[4-(methoxymethoxy)phenyl]butanoic acid		C₁₂H₁₆O₄	详情	详情
(XIV)	55603			C₃₀H₃₀O₂Si₂	详情	详情
(XV)	55604			C₉₀H₈₄Li₃O₆Si₆Sm	详情	详情
(XVI)	39749	3,4-dihydroxybenzaldehyde	139-85-5	C₇H₆O₃	详情	详情
(XVII)	55602	3,4-bis{[tert-butyl(dimethyl)silyl]oxy}benzaldehyde		C₁₉H₃₄O₃Si₂	详情	详情
(XVIII)	55605	(1R)-1-(3,4-bis{[tert-butyl(dimethyl)silyl]oxy}phenyl)-2-nitro-1-ethanol		C₂₀H₃₇NO₅Si₂	详情	详情
(XIX)	55606	(1R)-2-amino-1-(3,4-bis{[tert-butyl(dimethyl)silyl]oxy}phenyl)-1-ethanol		C₂₀H₃₉NO₃Si₂	详情	详情
(XX)	55607	N-[(2R)-2-(3,4-bis{[tert-butyl(dimethyl)silyl]oxy}phenyl)-2-hydroxyethyl]-4-[4-(methoxymethoxy)phenyl]butanamide		C₃₂H₅₃NO₆Si₂	详情	详情
(XXI)	55608	(1R)-1-(3,4-bis{[tert-butyl(dimethyl)silyl]oxy}phenyl)-2-({4-[4-(methoxymethoxy)phenyl]butyl}amino)-1-ethanol		C₃₂H₅₅NO₅Si₂	详情	详情

Extended Information