methyl 2-(3-hydroxyphenyl)acetate -Drug Synthesis Database

【结构式】

【分子编号】58567

【品名】methyl 2-(3-hydroxyphenyl)acetate

【CA登记号】

【分子式】C₉H₁₀O₃

【分子量】166.1766

【元素组成】C 65.05% H 6.07% O 28.88%

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：(XI)

In a solution-phase synthesis, 2,2-diphenylethylamine (VI) was reductively condensed with 2-chloro-3-(trifluoromethyl)benzaldehyde (VIII) using a polymer-supported borohydride resin to give the secondary amine (X). Mitsunobu coupling of methyl 3-hydroxyphenylacetate (XI) with 3-bromo-1-propanol (IV) afforded the bromopropyl ether (XII). Condensation of bromide (XII) with amine (X) in refluxing acetonitrile furnished amino ester (XIII). This was finally hydrolyzed with LiOH to the title carboxylic acid.

参考文献中间体

合成目标

【1】 Willson, T.M.; Collins, J.L.; Maloney, P.R.; Fivush, A.M.; Stewart, E.L. (GlaxoSmithKline plc); Chemical cpds.. WO 0224632 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IV)	12573	3-Bromo-1-propanol; 3-Bromopropanol	627-18-9	C₃H₇BrO	详情	详情
(VI)	38962	2,2-diphenylethylamine; 2,2-diphenyl-1-ethanamine	3963-62-0	C₁₄H₁₅N	详情	详情
(VIII)	58564	2-chloro-3-trifluoromethyl benzaldehyde	93118-03-7	C₈H₄ClF₃O	详情	详情
(X)	58566	N-[2-chloro-3-(trifluoromethyl)benzyl]-2,2-diphenyl-1-ethanamine; N-[2-chloro-3-(trifluoromethyl)benzyl]-N-(2,2-diphenylethyl)amine		C₂₂H₁₉ClF₃N	详情	详情
(XI)	58567	methyl 2-(3-hydroxyphenyl)acetate		C₉H₁₀O₃	详情	详情
(XII)	58568	methyl 2-[3-(3-bromopropoxy)phenyl]acetate		C₁₂H₁₅BrO₃	详情	详情
(XIII)	58569	methyl 2-(3-{3-[[2-chloro-3-(trifluoromethyl)benzyl](2,2-diphenylethyl)amino]propoxy}phenyl)acetate		C₃₄H₃₃ClF₃NO₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IX)

Claisen rearrangement of allyl ether (I) in refluxing o-dichlorobenzene affords (II). The allyl group of (II) is subsequently hydrogenated over Pd/C to provide the propyl derivative (III). Benzophenone (III) is converted into the corresponding oxime (IV) by means of hydroxylamine hydrochloride and NaOAc. Acetylation of oxime (IV), followed by refluxing in pyridine gives rise to the benzisoxazole (V). The phenolic hydroxyl group of (V) is then alkylated by 1,4-dibromobutane (VI) producing the bromobutyl ether (VII). 3-Hydroxyphenylacetic acid (VIII) is esterified with MeOH/H2SO4 to give the methyl ester (IX). This is then condensed with bromide (VII) in the presence of K2CO3 to furnish diether (X). Finally, saponification of the methyl ester group of (X) employing LiOH yields the target carboxylic acid (1,2)

参考文献中间体

合成目标

【1】 Adams, A.D.; Yuen, W.; Hu, Z.; Santini, C.; Jones, A.B.; MacNaul, K.L.; Berger, J.P.; Doebber, T.W.; Moller, D.E.; Amphipathic 3-phenyl-7-propylbenzisoxazoles; human PPAR gamma, delta and alpha agonists. Bioorg Med Chem Lett 2003, 13, 5, 931.
【2】 Adams, A.D.; Berger, J.P.; Berger, G.D.; Fitch, K.J.; Graham, D.W.; Jones, A.B.; Von Langen, D.; Leibowitz, M.D.; Moller, D.E.; Patchett, A.A.; Santini, C.; Sahoo, S.P.; Tolman, R.L.; Toupence, R.B.; Walsh, T.F. (Merck & Co., Inc.); Heterocyclic derivs. as antidiabetic and antiobesity agents. EP 0882029; JP 2002503203; US 6090836; WO 9728137 .

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)	63548	[4-(allyloxy)-2-hydroxyphenyl](phenyl)methanone		C₁₆H₁₄O₃	详情	详情
(II)	63549	(3-allyl-2,4-dihydroxyphenyl)(phenyl)methanone		C₁₆H₁₄O₃	详情	详情
(III)	63550	(2,4-dihydroxy-3-propylphenyl)(phenyl)methanone		C₁₆H₁₆O₃	详情	详情
(IV)	63551	(2,4-dihydroxy-3-propylphenyl)(phenyl)methanone oxime		C₁₆H₁₇NO₃	详情	详情
(V)	63552	3-phenyl-7-propyl-1,2-benzisoxazol-6-ol		C₁₆H₁₅NO₂	详情	详情
(VI)	11883	1,4-Dibromobutane; 1,4-Butylene bromide	110-52-1	C₄H₈Br₂	详情	详情
(VII)	63553	6-(4-bromobutoxy)-3-phenyl-7-propyl-1,2-benzisoxazole; 4-bromobutyl 3-phenyl-7-propyl-1,2-benzisoxazol-6-yl ether		C₂₀H₂₂BrNO₂	详情	详情
(VIII)	58561	2-(3-hydroxyphenyl)acetic acid		C₈H₈O₃	详情	详情
(IX)	58567	methyl 2-(3-hydroxyphenyl)acetate		C₉H₁₀O₃	详情	详情
(X)	63554	methyl 2-(3-{4-[(3-phenyl-7-propyl-1,2-benzisoxazol-6-yl)oxy]butoxy}phenyl)acetate		C₂₉H₃₁NO₅	详情	详情

Extended Information