1-iodo-4-methoxybenzene; 4-iodophenyl methyl ether -Drug Synthesis Database

【结构式】

【分子编号】31009

【品名】1-iodo-4-methoxybenzene; 4-iodophenyl methyl ether

【CA登记号】696-62-8

【分子式】C₇H₇IO

【分子量】234.03645

【元素组成】C 35.92% H 3.01% I 54.22% O 6.84%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(I)

The reaction of 4-methoxyphenyl iodide (I) with trimethylvinyllsilane (II) and 3,5-dimethoxyphenyl iodide (III) by means of Pd(dba)2, KF, tetrabutylammonium chloride (TBAC) and K2CO3 in toluene gives the trimethoxystilbene (IV), which is finally demethylated by reaction with BCl3 and tetrabutylammonium iodide (TBAI) in dichloromethane to afford the target Resveratrol.

参考文献中间体

合成目标

【1】 Jeffery, T.; Ferber, B.; One-pot palladium-catalyzed highly chemo-, regio-, and stereoselective synthesis of trans-stilbene derivatives. A concise and convenient synthesis of resveratrol. Tetrahedron Lett 2003, 44, 1, 193.

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)	31009	1-iodo-4-methoxybenzene; 4-iodophenyl methyl ether	696-62-8	C₇H₇IO	详情	详情
(II)	62022	Vinyltrimethylsilane; Ethenyltrimethylsilane; Trimethylvinylsilane; TRIMETHYL(VINYL)SILANE; (Trimethylsilyl)ethylene; Vinyltrimethylsilane; Vinyl-trimethylsilan; (Trimethylsilyl)ethylene; (ETHENYLTRIMETHYLSILANE, TRIMETHYLVINYLSILANE)	754-05-2	C₅H₁₂Si	详情	详情
(III)	62023	3-iodo-5-methoxyphenyl methyl ether; 1-iodo-3,5-dimethoxybenzene		C₈H₉IO₂	详情	详情
(IV)	62024	4-[(E)-2-(3,5-dimethoxyphenyl)ethenyl]phenyl methyl ether; 1,3-dimethoxy-5-[(E)-2-(4-methoxyphenyl)ethenyl]benzene		C₁₇H₁₈O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

The condensation of 1-benzyl-4-piperidone (I) with 4-iodoanisole (II) in ethyl ether gives 1-benzyl-4-(2-methoxyphenyl)piperidin-4-ol (III), which is dehydrated by means of p-toluenesulfonic acid in refluxing toluene yielding the tetrahydropyridine (IV). The hydroboration of (IV) with NaBH4 and BF3 ethearate in dimethoxyethane affords trans-1-benzyl-4-(2-methoxyphenyl)piperidin-3-ol (V), which is treated with BBr3 in dichloromethane to give the 4-hydroxyphenyl derivative (VI). The hydrogenolysis of (VI) with H2 over Pd/C in methanol yields trans-4-(2-hydroxyphenyl)piperidin-3-ol (VII), which is treated with tert-butoxycarbonyl anhydride and triethylamine in DMF to afford the carbamate (VIII). The condensation of 3-chloropropyl-(2-methoxyphenyl)ether (IX) (obtained by the NaH promoted condensation of 2-methoxybenzyl chloride (X) and 3-chloropropanol (XI)) with (VIII) by means of K2CO3 in hot 2-butanone gives the expected phenolic ether (XII), which is condensed with 7-(bromomethyl)quinoline (XIII) by means of NaH in DMF yielding the piperidinyl ether (XIV). The selective hydrogenation of (XIV) with NiCl2 and NaBH4 in methanol affords the tetrahydroquinoline derivative (XV), which is finally treated with HCl in methanol to eliminate the carbamate protecting group.

参考文献中间体

合成目标

【1】 Breu, V.; Guller, R.; Binggeli, A.; et al.; Piperidine-renin inhibitors compounds with improved physicochemical properties. Bioorg Med Chem Lett 1999, 9, 10, 1403.
【2】 Binggeli, A.; Breu, V.; Bur, D.; Fischli, W.; Gueller, R.; Hirth, G.; Maerki, H.-P.; Mueller, M.; Oefner, C.; Stadler, H.; Vieira, E.; Wilhelm, M.; Wostl, W. (F. Hoffmann-La Roche AG); New 4-(oxyalkoxyphenyl)-3-oxy-piperidines for treating heart and kidney insufficiency. EP 0863875; JP 1999500447; WO 9709311 .

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)	15720	1-benzyltetrahydro-4(1H)-pyridinone; 1-Benzyl-4-piperidone; N-Benzyl-4-piperidone; 1-(benzyl)-4-piperidinone; 1-benzylpiperidin-4-one; 1-(benzyl)piperidin-4-one	3612-20-2	C₁₂H₁₅NO	详情	详情
(II)	31009	1-iodo-4-methoxybenzene; 4-iodophenyl methyl ether	696-62-8	C₇H₇IO	详情	详情
(III)	31010	4-(1-benzyl-4-methyl-4-piperidinyl)phenyl methyl ether; 1-benzyl-4-(4-methoxyphenyl)-4-methylpiperidine		C₂₀H₂₅NO	详情	详情
(IV)	31011	4-(1-benzyl-1,2,3,6-tetrahydro-4-pyridinyl)phenyl methyl ether; 1-benzyl-4-(4-methoxyphenyl)-1,2,3,6-tetrahydropyridine		C₁₉H₂₁NO	详情	详情
(V)	31012	(3R,4R)-1-benzyl-4-(4-methoxyphenyl)-3-piperidinol		C₁₉H₂₃NO₂	详情	详情
(VI)	31013	(3R,4R)-1-benzyl-4-(4-hydroxyphenyl)-3-piperidinol		C₁₈H₂₁NO₂	详情	详情
(VII)	31014	(3R,4R)-4-(4-hydroxyphenyl)-3-piperidinol		C₁₁H₁₅NO₂	详情	详情
(VIII)	31015	tert-butyl (3R,4R)-3-hydroxy-4-(4-hydroxyphenyl)-1-piperidinecarboxylate		C₁₆H₂₃NO₄	详情	详情
(IX)	31016	1-[(3-chloropropoxy)methyl]-2-methoxybenzene; 2-[(3-chloropropoxy)methyl]phenyl methyl ether		C₁₁H₁₅ClO₂	详情	详情
(X)	31017	2-(chloromethyl)phenyl methyl ether; 1-(chloromethyl)-2-methoxybenzene	7035-02-1	C₈H₉ClO	详情	详情
(XI)	19490	3-chloro-1-propanol	627-30-5	C₃H₇ClO	详情	详情
(XII)	31018	tert-butyl (3R,4R)-3-hydroxy-4-(4-[3-[(2-methoxybenzyl)oxy]propoxy]phenyl)-1-piperidinecarboxylate		C₂₇H₃₇NO₆	详情	详情
(XIII)	31019	7-(bromomethyl)quinoline		C₁₀H₈BrN	详情	详情
(XIV)	31020	tert-butyl (3R,4R)-4-(4-[3-[(2-methoxybenzyl)oxy]propoxy]phenyl)-3-(7-quinolinylmethoxy)-1-piperidinecarboxylate		C₃₇H₄₄N₂O₆	详情	详情
(XV)	31021	tert-butyl (3R,4R)-4-(4-[3-[(2-methoxybenzyl)oxy]propoxy]phenyl)-3-(1,2,3,4-tetrahydro-7-quinolinylmethoxy)-1-piperidinecarboxylate		C₃₇H₄₈N₂O₆	详情	详情

合成路线3

该中间体在本合成路线中的序号：(III)

1,12-Dicarba-closo-dodecaborane (I) was lithiated with n-butyllithium in 1,2-dimethoxyethane and subsequently converted to the C-copper(I) derivative (II) with cuprous chloride. Coupling of (II) with p-iodoanisole (III) in the presence of pyridine furnished the C-arylated compound (IV). This was converted to the C-methoxycarbonyl derivative (V) via formation of the corresponding lithiocarborane, and then treatment with methyl chloroformate. Reduction of the methyl ester group with LiAlH4 produced alcohol (VI). Finally, cleavage of the methyl ether by means of boron tribromide yielded the title compound.

参考文献中间体

合成目标

【1】 Fukasawa, H.; Endo, Y.; Shudo, K.; Yamakoshi, Y.; Yamaguchi, M.; Iijima, T.; Potent estrogenic agonists bearing dicarba-closo-dodecaborane as a hydrophobic pharmacophore. J Med Chem 1999, 42, 9, 1501.
【2】 Endo, Y.; et al.; Structure-activity of estrogenic agonists bearing dicarba-closo-dodecarbone. Effect of geometry and separation distance of hydroxyl groups at the ends of molecules. Bioorg Med Chem Lett 1999, 9, 23, 3313.

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)	42007	3-[6-(1,2-diboriran-3-yl)hexaboranyl]-1,2-diborirane		C₂H₁₂B₁₀	详情	详情
(II)	42008	[3-[6-(1,2-diboriran-3-yl)hexaboranyl]-1,2-diboriran-3-yl]copper		C₂H₁₁B₁₀Cu	详情	详情
(III)	31009	1-iodo-4-methoxybenzene; 4-iodophenyl methyl ether	696-62-8	C₇H₇IO	详情	详情
(IV)	42009	3-[6-(1,2-diboriran-3-yl)hexaboranyl]-3-(4-methoxyphenyl)-1,2-diborirane; 4-[3-[6-(1,2-diboriran-3-yl)hexaboranyl]-1,2-diboriran-3-yl]phenyl methyl ether		C₉H₁₈B₁₀O	详情	详情
(V)	42010	methyl 3-[6-[3-(4-methoxyphenyl)-1,2-diboriran-3-yl]hexaboranyl]-1,2-diborirane-3-carboxylate		C₁₁H₂₀B₁₀O₃	详情	详情
(VI)	42011	(3-[6-[3-(4-methoxyphenyl)-1,2-diboriran-3-yl]hexaboranyl]-1,2-diboriran-3-yl)methanol		C₁₀H₂₀B₁₀O₂	详情	详情

Extended Information