3-bromo-2,5-dimethoxybenzaldehyde -Drug Synthesis Database

【结构式】

【分子编号】25603

【品名】3-bromo-2,5-dimethoxybenzaldehyde

【CA登记号】

【分子式】C₉H₉BrO₃

【分子量】245.07266

【元素组成】C 44.11% H 3.7% Br 32.6% O 19.59%

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：(II)

1. The Suzuki coupling of arylboronic acid (I) with 3-bromo-2,5-dimethoxybenzaldehyde (II) with concomitant desilylation provided biphenyl aldehyde (III). After protection of the phenolic hydroxyl as the mesylate (IV), selective bromination of (IV) in the presence of NaOAc in AcOH provided bromoaldehyde (V). A Baeyer-Villiger oxidation of the aldehyde group of (V) with m-chloroperbenzoic acid, followed by acid hydrolysis of the intermediate formate ester, produced phenol (VI). which was coupled with protected boronic acid (VII) in the presence of Pd(PPh3)4 to yield terphenyl (VIII). Mesylation of the hydroxyl groups of (VIII) and further hydrogenolytic cleavage of the benzyl ether gave phenol (X). Then, alkylationof (X) with prenyl bromide (XI) provided prenyl ether (XII). The mesylate groups of (XII) were finally removed by hydrolysis with KOH to furnish the title compound.

参考文献中间体

合成目标

【1】 Yonezawa, S.; et al.; Total synthesis of terprenin, a novel immunosuppressive p-terphenyl derivative. J Org Chem 1998, 63, 17, 5831.
【2】 Nagashima, K.; Kamigauchi, T.; Sakazaki, R.; et al.; Terprenins, novel immunosuppressants produced by Aspergillus candidus. J Antibiot 1998, 51, 4, 445.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	25602	4-[[tert-butyl(dimethyl)silyl]oxy]phenylboronic acid	C₁₂H₂₁BO₃Si	详情	详情
(II)	25603	3-bromo-2,5-dimethoxybenzaldehyde	C₉H₉BrO₃	详情	详情
(III)	25604	4'-hydroxy-2,5-dimethoxy[1,1'-biphenyl]-3-carbaldehyde	C₁₅H₁₄O₄	详情	详情
(IV)	25605	3'-formyl-2',5'-dimethoxy[1,1'-biphenyl]-4-yl methanesulfonate	C₁₆H₁₆O₆S	详情	详情
(V)	25606	4'-bromo-3'-formyl-2',5'-dimethoxy[1,1'-biphenyl]-4-yl methanesulfonate	C₁₆H₁₅BrO₆S	详情	详情
(VI)	25607	4'-bromo-3'-hydroxy-2',5'-dimethoxy[1,1'-biphenyl]-4-yl methanesulfonate	C₁₅H₁₅BrO₆S	详情	详情
(VII)	25608	4-(benzyloxy)-3-[[tert-butyl(dimethyl)silyl]oxy]phenylboronic acid	C₁₉H₂₇BO₄Si	详情	详情
(VIII)	25609	Methanesulfonic acid 4''-benzyloxy-3',3''-dihydroxy-2',5'-dimethoxy-p-terphenyl-4-yl ester	C₂₈H₂₆O₈S	详情	详情
(IX)	25610	4-Benzyloxy-3',6'-dimethoxy-p-terphenyl-3,2',4''-triol tris methanesuolfonyl ester	C₃₀H₃₀O₁₂S₃	详情	详情
(X)	25611	3',6'-Dimethoxy-p-terphenyl-2',3,4,4''-tetrol 2'-O,3-O,4''-O-tris methanesulfonate	C₂₃H₂₄O₁₂S₃	详情	详情
(XII)	25612	3',6'-Dimethoxy-4-(3-methyl-2-butenyloxy)-p-terphenyl-2',3,4''-triol tris methanesulfonate	C₂₈H₃₂O₁₂S₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

2. In an alternative synthesis, 5-bromosalicylaldehyde (XIII) was alkylated with bromoacetaldehyde dimethyl acetal (XIV) to afford ether (XV). Further Baeyer-Villiger reaction with (XV) produced phenol (XVI), which was cyclized to the benzodioxine (XVII) with p-TsOH. Lithiation of (XVII), followed by reaction with triisopropyl borate and hydrolytic work-up, gave boronic acid (XVIII). Aldehyde (II) was treated with MCPBA yielding phenol (XIII), which was iodinated in the presence of tert-butylamine to give the bromo iodo derivative (XIV). Sequential Suzuki coupling of bromo iodo compound (XIV) with boronic acid (XVIII) yielding (XIX), and then with boronic acid (I) provided terphenyl (XX). Hydrolysis of the methyl acetal of (XX) using p-TsOH gave cyclic hemiacetal (XXI). Finally, Wittig reaction of (XXI) with the phosphorane prepared from isopropyl triphenylphosphonium iodide and n-BuLi provided the title compound.

参考文献中间体

合成目标

【1】 Yonezawa, S.; et al.; Total synthesis of terprenin, a novel immunosuppressive p-terphenyl derivative. J Org Chem 1998, 63, 17, 5831.
【2】 Nagashima, K.; Kamigauchi, T.; Sakazaki, R.; et al.; Terprenins, novel immunosuppressants produced by Aspergillus candidus. J Antibiot 1998, 51, 4, 445.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XIIIa)	25618	3-bromo-2,5-dimethoxyphenol		C₈H₉BrO₃	详情	详情
(XIVb)	25619	3-bromo-6-iodo-2,5-dimethoxyphenol		C₈H₈BrIO₃	详情	详情
(I)	25602	4-[[tert-butyl(dimethyl)silyl]oxy]phenylboronic acid		C₁₂H₂₁BO₃Si	详情	详情
(II)	25603	3-bromo-2,5-dimethoxybenzaldehyde		C₉H₉BrO₃	详情	详情
(XIII)	25613	5-bromo-2-hydroxybenzaldehyde; 5-Bromosalicylaldehyde	1761-61-1	C₇H₅BrO₂	详情	详情
(XIV)	13183	2-Bromo-1,1-dimethoxyethane; 2-Bromo-1-methoxyethyl methyl ether; Bromoacetaldehyde dimethyl acetal	7252-83-7	C₄H₉BrO₂	详情	详情
(XV)	25614	5-bromo-2-(2,2-dimethoxyethoxy)benzaldehyde		C₁₁H₁₃BrO₄	详情	详情
(XVI)	25615	5-bromo-2-(2,2-dimethoxyethoxy)phenol		C₁₀H₁₃BrO₄	详情	详情
(XVII)	25616	7-bromo-2,3-dihydro-1,4-benzodioxin-2-yl methyl ether		C₉H₉BrO₃	详情	详情
(XVIII)	25617	3-methoxy-2,3-dihydro-1,4-benzodioxin-6-ylboronic acid		C₉H₁₁BO₅	详情	详情
(XIX)	25620	3-bromo-2,5-dimethoxy-6-(3-methoxy-2,3-dihydro-1,4-benzodioxin-6-yl)phenol		C₁₇H₁₇BrO₆	详情	详情
(XX)	25621	2,5-dimethoxy-4-(3-methoxy-2,3-dihydro-1,4-benzodioxin-6-yl)[1,1'-biphenyl]-3,4'-diol		C₂₃H₂₂O₇	详情	详情
(XXI)	25622	4-(3-hydroxy-2,3-dihydro-1,4-benzodioxin-6-yl)-2,5-dimethoxy[1,1'-biphenyl]-3,4'-diol		C₂₂H₂₀O₇	详情	详情

Extended Information