2,6-dimethoxyphenol -Drug Synthesis Database

【结构式】

【分子编号】20228

【品名】2,6-dimethoxyphenol

【CA登记号】91-10-1

【分子式】C₈H₁₀O₃

【分子量】154.1656

【元素组成】C 62.33% H 6.54% O 31.13%

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：(VI)

By condensation of 2-aminomethyl-1,4-benzodioxane (I) with 2,6-dimethoxyphenoxyethyl chloride (II) performed by heating at 160 C or by means of K2CO3 in refluxing CHCl3 - water. The starting products (I) and (II) are prepared as follows: 1) The reaction of 2-chloromethyl-1,4-benzodioxane (III) with potassium phthalimide (IV) in refluxing DMF gives 2-phthalimidomethyl-1,4-benzodioxane (V), which is then treated with hydrazine hydrate (A) in refluxing 2-ethoxyethanol to give (I). 2) The condensation of 2,6-dimethoxyphenol (VI) with ethylene carbonate (VII) by means of K2CO3 in refluxing toluene gives 2,6-dimethoxyphenoxyethanol (VIII), which is then refluxed with SOCl2 to afford (II).

参考文献中间体

合成目标

【1】 US 3472874 .
【2】 Castaner, J.; Serradell, M.N.; Hillier, K.; Blancafort, P.; WB-4101. Drugs Fut 1979, 4, 5, 369.
【3】 Green, P.N.; et al.; Synthesis and pharmacological properties of a series of 2-(substituted-aminoethyl)-1,4-benzodioxanes. J Med Chem 1969, 12, 2, 326-329.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	27334	N-(2,5-dichloropentyl)-2-methoxy-5-[methyl(methylsulfonyl)amino]benzamide		C₁₅H₂₂Cl₂N₂O₄S	详情	详情
(I)	39477	2,3-dihydro-1,4-benzodioxin-2-ylmethanamine; 2,3-dihydro-1,4-benzodioxin-2-ylmethylamine		C₉H₁₁NO₂	详情	详情
(II)	39479	2-(2-chloroethoxy)-1,3-dimethoxybenzene; 2-(2-chloroethoxy)-3-methoxyphenyl methyl ether		C₁₀H₁₃ClO₃	详情	详情
(III)	39475	2-(chloromethyl)-2,3-dihydro-1,4-benzodioxine	2164-33-2	C₉H₉ClO₂	详情	详情
(IV)	27890	Potassium phthalimide	1074-82-4	C₈H₄KNO₂	详情	详情
(V)	39476	2-(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)-1H-isoindole-1,3(2H)-dione		C₁₇H₁₃NO₄	详情	详情
(VI)	20228	2,6-dimethoxyphenol	91-10-1	C₈H₁₀O₃	详情	详情
(VII)	32802	1,3-dioxolan-2-one	96-49-1	C₃H₄O₃	详情	详情
(VIII)	39478	2-(2,6-dimethoxyphenoxy)-1-ethanol		C₁₀H₁₄O₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

The Grignard reaction of ethyl heptanoate (I) with deuterated methylmagnesium iodide (II) in ether gives deuterated 2-methyl-2-octanol (III), which is treated with deuterium oxide to yield heptadeuterated 2-methyl-2-octanol (IV). The condensation of (IV) with monodeuterated 2,6-dimethoxyphenol (V) (obtained by treatment of 2,6-dimethoxyphenol (VI) with deuterium oxide) by means of deuterated trifluoromethylsulfonic acid affords the alkylated phenol (VII), which is phosphorylated with diethyl phosphite and triethylamine giving the phosphate (VIII). The reduction of (VIII) with Li/NH3 yields the deuterated dimethoxybenzene (IX), which is demethylated with boron tribromide in dichloromethane to afford the deuterated resorcinol (X). The condensation of (X) with alpha-pinene-3,10-diol 10-O-pivalic ester (XI) by means of boron trifluoride etherate in methylene chloride gives the deuterated target compound as its monopivalic ester (XII), which is finally treated with LiAlH4 in THF to eliminate the ester group.

参考文献中间体

合成目标

【1】 Pop, E.; et al.; Synthesis of deuterated dexanabinol, a nonpsychotropic cannabinoid with neuroprotective properties. J Label Compd Radiopharm 1998, 41, 10, 885.

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)	20224	ethyl heptanoate	106-30-9	C₉H₁₈O₂	详情	详情
(II)	20225	iodo(methyl)magnesium	917-64-6	CH₃IMg	详情	详情
(II)	63794	iodo(methyl)magnesium		CH₃IMg	详情	详情
(III)	20226	2-methyl-2-octanol		C₉H₂₀O	详情	详情
(III)	63795	2-methyl-2-octanol		C₉H₂₀O	详情	详情
(IV)	20226	2-methyl-2-octanol		C₉H₂₀O	详情	详情
(IV)	63796	2-methyl-2-octanol		C₉H₂₀O	详情	详情
(V)	20228	2,6-dimethoxyphenol	91-10-1	C₈H₁₀O₃	详情	详情
(V)	63797	2,6-dimethoxyphenol	91-10-1	C₈H₁₀O₃	详情	详情
(VI)	20228	2,6-dimethoxyphenol	91-10-1	C₈H₁₀O₃	详情	详情
(VII)	20230	4-(1,1-dimethylheptyl)-2,6-dimethoxyphenol		C₁₇H₂₈O₃	详情	详情
(VII)	63798	4-(1,1-dimethylheptyl)-2,6-dimethoxyphenol		C₁₇H₂₈O₃	详情	详情
(VIII)	20231	4-(1,1-dimethylheptyl)-2,6-dimethoxyphenyl diethyl phosphate		C₂₁H₃₇O₆P	详情	详情
(VIII)	63799	4-(1,1-dimethylheptyl)-2,6-dimethoxyphenyl diethyl phosphate		C₂₁H₃₇O₆P	详情	详情
(IX)	20232	1-(1,1-dimethylheptyl)-3,5-dimethoxybenzene; 3-(1,1-dimethylheptyl)-5-methoxyphenyl methyl ether		C₁₇H₂₈O₂	详情	详情
(IX)	63800	3-(1,1-dimethylheptyl)-5-methoxyphenyl methyl ether; 1-(1,1-dimethylheptyl)-3,5-dimethoxybenzene		C₁₇H₂₈O₂	详情	详情
(X)	20233	5-(1,1-dimethylheptyl)-1,3-benzenediol		C₁₅H₂₄O₂	详情	详情
(X)	63601	methyl (3aR,4R,5S,5aR,10bR,13aR)-4-(acetyloxy)-3a-ethyl-9-[(13S,15S)-17-ethyl-13-(methoxycarbonyl)-1,11-diazatetracyclo[13.3.1.0~4,12~.0~5,10~]nonadeca-4(12),5,7,9,17-pentaen-13-yl]-5-hydroxy-8-methoxy-6-methyl-3a,4,5,5a,6,11,12,13a-octahydro-1H-indolizino[8,1-cd]carbazole-5-carboxylate		C₄₆H₅₆N₄O₈	详情	详情
(XI)	20234	(4-hydroxy-6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl)methyl pivalate		C₁₅H₂₄O₃	详情	详情
(XII)	20235	[(6aS,10aS)-3-(1,1-dimethylheptyl)-1-hydroxy-6,6-dimethyl-6a,7,10,10a-tetrahydro-6H-benzo[c]chromen-9-yl]methyl pivalate		C₃₀H₄₆O₄	详情	详情
(XII)	63802	[(6aS,10aS)-3-(1,1-dimethylheptyl)-1-hydroxy-6,6-dimethyl-6a,7,10,10a-tetrahydro-6H-benzo[c]chromen-9-yl]methyl pivalate		C₃₀H₄₆O₄	详情	详情

合成路线3

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】 Pop, E.; et al.; Synthesis of deuterated dexanabinol, a nonpsychotropic cannabinoid with neuroprotective properties. J Label Compd Radiopharm 1998, 41, 10, 885.

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)	20224	ethyl heptanoate	106-30-9	C₉H₁₈O₂	详情	详情
(II)	20225	iodo(methyl)magnesium	917-64-6	CH₃IMg	详情	详情
(II)	63794	iodo(methyl)magnesium		CH₃IMg	详情	详情
(III)	20226	2-methyl-2-octanol		C₉H₂₀O	详情	详情
(III)	63795	2-methyl-2-octanol		C₉H₂₀O	详情	详情
(IV)	20226	2-methyl-2-octanol		C₉H₂₀O	详情	详情
(IV)	63796	2-methyl-2-octanol		C₉H₂₀O	详情	详情
(V)	20228	2,6-dimethoxyphenol	91-10-1	C₈H₁₀O₃	详情	详情
(V)	63797	2,6-dimethoxyphenol	91-10-1	C₈H₁₀O₃	详情	详情
(VI)	20228	2,6-dimethoxyphenol	91-10-1	C₈H₁₀O₃	详情	详情
(VII)	20230	4-(1,1-dimethylheptyl)-2,6-dimethoxyphenol		C₁₇H₂₈O₃	详情	详情
(VII)	63798	4-(1,1-dimethylheptyl)-2,6-dimethoxyphenol		C₁₇H₂₈O₃	详情	详情
(VIII)	20231	4-(1,1-dimethylheptyl)-2,6-dimethoxyphenyl diethyl phosphate		C₂₁H₃₇O₆P	详情	详情
(VIII)	63799	4-(1,1-dimethylheptyl)-2,6-dimethoxyphenyl diethyl phosphate		C₂₁H₃₇O₆P	详情	详情
(IX)	20232	1-(1,1-dimethylheptyl)-3,5-dimethoxybenzene; 3-(1,1-dimethylheptyl)-5-methoxyphenyl methyl ether		C₁₇H₂₈O₂	详情	详情
(IX)	63800	3-(1,1-dimethylheptyl)-5-methoxyphenyl methyl ether; 1-(1,1-dimethylheptyl)-3,5-dimethoxybenzene		C₁₇H₂₈O₂	详情	详情
(X)	20233	5-(1,1-dimethylheptyl)-1,3-benzenediol		C₁₅H₂₄O₂	详情	详情
(X)	63601	methyl (3aR,4R,5S,5aR,10bR,13aR)-4-(acetyloxy)-3a-ethyl-9-[(13S,15S)-17-ethyl-13-(methoxycarbonyl)-1,11-diazatetracyclo[13.3.1.0~4,12~.0~5,10~]nonadeca-4(12),5,7,9,17-pentaen-13-yl]-5-hydroxy-8-methoxy-6-methyl-3a,4,5,5a,6,11,12,13a-octahydro-1H-indolizino[8,1-cd]carbazole-5-carboxylate		C₄₆H₅₆N₄O₈	详情	详情
(XI)	20234	(4-hydroxy-6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl)methyl pivalate		C₁₅H₂₄O₃	详情	详情
(XII)	20235	[(6aS,10aS)-3-(1,1-dimethylheptyl)-1-hydroxy-6,6-dimethyl-6a,7,10,10a-tetrahydro-6H-benzo[c]chromen-9-yl]methyl pivalate		C₃₀H₄₆O₄	详情	详情
(XII)	63802	[(6aS,10aS)-3-(1,1-dimethylheptyl)-1-hydroxy-6,6-dimethyl-6a,7,10,10a-tetrahydro-6H-benzo[c]chromen-9-yl]methyl pivalate		C₃₀H₄₆O₄	详情	详情

Extended Information