methyl 4-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthalenyl)carbonyl]benzoate -Drug Synthesis Database

【结构式】

【分子编号】35218

【品名】methyl 4-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthalenyl)carbonyl]benzoate

【CA登记号】

【分子式】C₂₄H₂₈O₃

【分子量】364.48452

【元素组成】C 79.09% H 7.74% O 13.17%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(V)

参考文献中间体

合成目标

【1】 ZhangL.Badea BA, Enyeart D,et aL 1995. Synthesis of isotopically labeled 4{1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydnr2-napluhyl) ethenyl] benzoic aci/l (LGD1069),apotent retinoid Xtecerjtor-se-lective Ligand.J LabeIComp Radiopharm, 36 (7): 701~712

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)	60250	1,1,4,4,7-pentamethyl-1,2,3,4-tetrahydro-2-naphthalenol		C₁₅H₂₂O	详情	详情
(II)	60251	1,1,4,4,6-pentamethyl-1,4-dihydronaphthalene		C₁₅H₂₀	详情	详情
(III)	35217	1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene		C₁₅H₂₂	详情	详情
(IV)	25029	p-Phthalic acid monomethyl ester chloride; Terephthalic acid monomethyl ester chloride; Methyl 4-chlorocarbonylbenzoate	7377-26-6	C₉H₇ClO₃	详情	详情
(V)	35218	methyl 4-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthalenyl)carbonyl]benzoate		C₂₄H₂₈O₃	详情	详情
(VI)	60246	methyl 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthalenyl)ethenyl]benzoate		C₂₅H₃₀O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

参考文献中间体

合成目标

【1】 Pfahl M, Zhang XK, Lehmann JM, et d.1994. RXR receptor homodimer formation and bridged bicycLic aromatic compounds and their use in modulating gene expresskm and screening modulating compounds W0 9412880

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)	25029	p-Phthalic acid monomethyl ester chloride; Terephthalic acid monomethyl ester chloride; Methyl 4-chlorocarbonylbenzoate	7377-26-6	C₉H₇ClO₃	详情	详情
(II)	35217	1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene		C₁₅H₂₂	详情	详情
(III)	35218	methyl 4-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthalenyl)carbonyl]benzoate		C₂₄H₂₈O₃	详情	详情
(IV)	60246	methyl 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthalenyl)ethenyl]benzoate		C₂₅H₃₀O₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(VI)

Treatment of 2,5-dimethyl-2-5-hexanediol (I) with dry hydrogen chloride in EtOH gives rise to the dichloro compound (II). Subsequent Friedel-Crafts condensation of dichloride (II) with toluene (III) in the presence of AlCl3 affords the tetrahydronaphthalene derivative (IV) (1). This is then condensed with mono-methyl terephthalic acid chloride (V) to produce ketone (VI). Wittig reaction of (VI) with methylene triphenylphosphorane leads to olefin (VII). Finally, alkaline hydrolysis of the methyl ester group of (VII) furnishes the target carboxylic acid

参考文献中间体

合成目标

【1】 Zhang, L.; Badea, B.A.; Enyeart, D.; Berger, E.M.; Mais, D.E.; Boehm, M.F.; Syntheses of isotopically labeled 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethenyl]benzoic acid (LGD1069), a potent retinoid X receptor-selective ligand. J Label Compd Radiopharm 1995, 36, 7, 701.
【2】 Boehm, M.F.; Heyman, R.A.; Zhi, L. (Ligand Pharmaceuticals, Inc.); Cpds. having selectivity for retinoid X receptors. EP 0983991; EP 0983992; JP 1996505359; JP 1996505852; JP 1996511027; US 5780676; US 5962731; WO 9321146; WO 9415902 .
【3】 Zhang, L.; Boehm, M.F.; Badea, B.A.; White, S.K.; Mais, D.E.; Berger, E.; Suto, C.M.; Goldman, M.E..; Heyman, R.A.; Synthesis and structure-activity relationships of novel retinoid X receptor-selective retinoids. J Med Chem 1994, 37, 18, 2930.

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)	60245	2,5-dimethyl-2,5-hexanediol		C₈H₁₈O₂	详情	详情
(II)	35216	2,5-dichloro-2,5-dimethylhexane		C₈H₁₆Cl₂	详情	详情
(III)	12890	Toluene	108-88-3	C₇H₈	详情	详情
(IV)	35217	1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene		C₁₅H₂₂	详情	详情
(V)	25029	p-Phthalic acid monomethyl ester chloride; Terephthalic acid monomethyl ester chloride; Methyl 4-chlorocarbonylbenzoate	7377-26-6	C₉H₇ClO₃	详情	详情
(VI)	35218	methyl 4-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthalenyl)carbonyl]benzoate		C₂₄H₂₈O₃	详情	详情
(VII)	60246	methyl 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthalenyl)ethenyl]benzoate		C₂₅H₃₀O₂	详情	详情

合成路线4

该中间体在本合成路线中的序号：(V)

Friedel-Crafts condensation of 2,5-dichloro-2,5-dimethylhexane (I) with toluene (II) in the presence of AlCl3 or FeCl3 afforded the tetrahydronaphthalene (III). Subsequent acylation of (III) with monomethyl terephthalic acid chloride (IV) provided keto ester (V), which was hydrolyzed to keto acid (VI) with methanolic KOH. Condensation of (VI) with hydroxylamine hydrochloride gave the corresponding oxime as a mixture of geometric isomers. The required Z isomer was then isolated by recrystallization from chloroform/hexane.

参考文献中间体

合成目标

【1】 Faul, M.M.; Ratz, A.M.; Sullivan, K.A.; Trankle, W.G.; Winneroski, L.L.; Synthesis of novel retinoid X receptor-selective retinoids. J Org Chem 2001, 66, 17, 5772.
【2】 Boehm, M.F.; Canan Koch, S.S.; Cesario, R.M.; Dardashti, L.J.; Nadzan, A.M.; Croston, G.E.; Heyman, R.A.; Synthesis of retinoid X receptor-specific ligands that are potent inducers of adipogenesis in 3T3-L1 cells. J Med Chem 1999, 42, 4, 742.
【3】 Zhang, L.; Boehm, M.F.; Badea, B.A.; White, S.K.; Mais, D.E.; Berger, E.; Suto, C.M.; Goldman, M.E..; Heyman, R.A.; Synthesis and structure-activity relationships of novel retinoid X receptor-selective retinoids. J Med Chem 1994, 37, 18, 2930.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	32201	Hydroxylamine	7803-49-8	H₃NO	详情	详情
(I)	35216	2,5-dichloro-2,5-dimethylhexane		C₈H₁₆Cl₂	详情	详情
(II)	12890	Toluene	108-88-3	C₇H₈	详情	详情
(III)	35217	1,1,4,4,6-pentamethyl-1,2,3,4-tetrahydronaphthalene		C₁₅H₂₂	详情	详情
(IV)	25029	p-Phthalic acid monomethyl ester chloride; Terephthalic acid monomethyl ester chloride; Methyl 4-chlorocarbonylbenzoate	7377-26-6	C₉H₇ClO₃	详情	详情
(V)	35218	methyl 4-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthalenyl)carbonyl]benzoate		C₂₄H₂₈O₃	详情	详情
(VI)	35219	4-[(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthalenyl)carbonyl]benzoic acid		C₂₃H₂₆O₃	详情	详情

Extended Information