2-(1-adamantyl)-4-bromophenol -Drug Synthesis Database

【结构式】

【分子编号】59536

【品名】2-(1-adamantyl)-4-bromophenol

【CA登记号】

【分子式】C₁₆H₁₉BrO

【分子量】307.23026

【元素组成】C 62.55% H 6.23% Br 26.01% O 5.21%

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：(III)

Friedel-Crafts condensation of 4-bromophenol (I) with 1-adamantanol (II) in the presence of H2SO4 yielded the adamantyl phenol (III). Subsequent alkylation of the sodium phenoxide of (III) with iodomethane produced the methyl ether (IV). The Grignard reagent (V), prepared from aryl bromide (IV), was converted to the organozincate derivative, and then subjected to a nickel-catalyzed cross-coupling with methyl 6-bromo-2-naphthoate (VI) to furnish adduct (VII). The target carboxylic acid was finally obtained by saponification of the methyl ester (VII).

参考文献中间体

合成目标

【1】 Charpentier, B.; et al.; Synthesis, structure-affinity relationships, and biological activities of ligands binding to retinoic acid receptor subtypes. J Med Chem 1995, 38, 26, 4993.
【2】 Shroot, B.; Eustache, J.; Bernardon, J.M. (Laboratoires Galderma SA); Benzonaphthalenic acid derivs., process for their preparation and their use in pharmacy and cosmetics. AU 9047961; EP 0199636; US 4717720; US 5098895; US 5183889 .

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)	25313	4-bromophenol	106-41-2	C₆H₅BrO	详情	详情
(II)	52642	1-Adamantanol; 1-Hydroxyadamantane; Tricyclo[3.3.1.1]decan-1-ol	768-95-6	C₁₀H₁₆O	详情	详情
(III)	59536	2-(1-adamantyl)-4-bromophenol		C₁₆H₁₉BrO	详情	详情
(IV)	59537	1-(5-bromo-2-methoxyphenyl)adamantane; 2-(1-adamantyl)-4-bromophenyl methyl ether		C₁₇H₂₁BrO	详情	详情
(V)	59538	[3-(1-adamantyl)-4-methoxyphenyl](bromo)magnesium		C₁₇H₂₁BrMgO	详情	详情
(VI)	59539	6-Bromo-2-naphthoic acid methyl ester; Methyl 6-bromo-2-naphthoate	33626-98-1	C₁₂H₉BrO₂	详情	详情
(VII)	59540	methyl 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoate		C₂₉H₃₀O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

Coupling between 4-bromophenol (I) and 1-adamantanol (II) in the presence of H2SO4 affords the adamantanyl phenol (III), which is further protected as the silyl ether (IV) by means of t-butyldimethylsilyl chloride and DMAP. Addition of triisopropyl borate to the organolithium derivative of (IV) gives rise, after aqueous quenching, to the boronic acid (V). Then, Suzuki coupling of boronic acid (V) with 6-bromopyridine-3-carbaldehyde (VI) furnishes the phenylpyridine adduct (VII). Desilylation of (VII) to provide phenol (VIII) is accomplished by treatment with tetrabutylammonium fluoride in THF. Finally, condensation of pyridine aldehyde (VIII) with 2,4-thiazolidinedione (IX) under Knoevenagel conditions provides the target compound

参考文献中间体

合成目标

【1】 Spruce, L.W.; Pfahl, M.; Fanjul, A.; Tachdjian, C.; Al-Shamma, H.A.; Pleynet, D.P.M.; Wiemann, T.R.; Ibarra, J.B. (Maxia Pharmaceuticals, Inc.); Heterocyclic derivs. for the treatment of cancer and other proliferative diseases. WO 02/072009 .

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)	25313	4-bromophenol	106-41-2	C₆H₅BrO	详情	详情
(II)	52642	1-Adamantanol; 1-Hydroxyadamantane; Tricyclo[3.3.1.1]decan-1-ol	768-95-6	C₁₀H₁₆O	详情	详情
(III)	59536	2-(1-adamantyl)-4-bromophenol		C₁₆H₁₉BrO	详情	详情
(IV)	59537	1-(5-bromo-2-methoxyphenyl)adamantane; 2-(1-adamantyl)-4-bromophenyl methyl ether		C₁₇H₂₁BrO	详情	详情
(V)	61340	3-(1-adamantyl)-4-{[tert-butyl(dimethyl)silyl]oxy}phenylboronic acid		C₂₂H₃₅BO₃Si	详情	详情
(VI)	61343	6-bromonicotinaldehyde		C₆H₄BrNO	详情	详情
(VII)	61341	6-(3-(1-adamantyl)-4-{[tert-butyl(dimethyl)silyl]oxy}phenyl)nicotinaldehyde		C₂₈H₃₇NO₂Si	详情	详情
(VIII)	61342	6-[3-(1-adamantyl)-4-hydroxyphenyl]nicotinaldehyde		C₂₂H₂₃NO₂	详情	详情
(IX)	10883	1,3-Thiazolane-2,4-dione; 2,4-Thiazolidinedione	2295-31-0	C₃H₃NO₂S	详情	详情

Extended Information