(3,5-dimethoxy-2,5-cyclohexadien-1-yl)methanol -Drug Synthesis Database

【结构式】

【分子编号】25566

【品名】(3,5-dimethoxy-2,5-cyclohexadien-1-yl)methanol

【CA登记号】

【分子式】C₉H₁₄O₃

【分子量】170.20836

【元素组成】C 63.51% H 8.29% O 28.2%

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：(II)

The reduction of 3,5-dimethoxybenzoic acid (I) first with Li in liquid NH3 and methanol, and then with LiAlH4 in THF gives 3,5-dimethoxy-1,4-dihydrobenzyl alcohol (II), which is cyclized with phenylhydrazine (III) in refluxing 4% sulfuric acid yielding 2-(hydroxymethyl)-1,2,3,4-tetrahydrocarbazol-4-one (IV). The reaction of (IV) with tosyl chloride in pyridine affords the corresponding tosylate (V), which is finally condensed with 4-(4-fluorobenzoyl)piperidine (VI) in N-methyl-2-pyrrolidone.

参考文献中间体

合成目标

【1】 Masaguer, C.F.; Formoso, E.; Raviña, E.; Tristán, H.; Loza, M.I.; Rivas, E.; Fontenla, J.A.; Butyrophenone analogues in the carbazole series: Synthesis and determination of affinities at D2 and 5-HT2A receptors. Bioorg Med Chem Lett 1998, 8, 24, 3571.

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)	22761	3,5-dimethoxybenzoic acid	1132-21-4	C₉H₁₀O₄	详情	详情
(II)	25566	(3,5-dimethoxy-2,5-cyclohexadien-1-yl)methanol		C₉H₁₄O₃	详情	详情
(III)	11818	Phenyl hydrazine; 1-Phenylhydrazine	100-63-0	C₆H₈N₂	详情	详情
(IV)	25567	2-(hydroxymethyl)-1,2,3,9-tetrahydro-4H-carbazol-4-one		C₁₃H₁₃NO₂	详情	详情
(V)	25568	(4-oxo-2,3,4,9-tetrahydro-1H-carbazol-2-yl)methyl 4-methylbenzenesulfonate		C₂₀H₁₉NO₄S	详情	详情
(VI)	21497	(4-Fluorophenyl)(4-piperidinyl)methanone; 4-(4-Fluorobenzoyl)piperidine; 4-(p-Fluorobenzoyl)piperidine	56346-57-7	C₁₂H₁₄FNO	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 reduction of 3,5-dimethoxybenzoic acid (I) first with Li in liquid NH3 and methanol, and then with LiAlH4 in THF gives 3,5-dimethoxy-1,4-dihydrobenzyl alcohol (II), which is cyclized with phenylhydrazine (III) in refluxing 4% sulfuric acid yielding 2-(hydroxymethyl)-1,2,3,4-tetrahydrocarbazol-4-one (IV). The reaction of (IV) with tosyl chloride in pyridine affords the corresponding tosylate (V), which is finally condensed with 4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine (VI) in N-methyl-2-pyrrolidone.

参考文献中间体

合成目标

【1】 Masaguer, C.F.; Formoso, E.; Raviña, E.; Tristán, H.; Loza, M.I.; Rivas, E.; Fontenla, J.A.; Butyrophenone analogues in the carbazole series: Synthesis and determination of affinities at D2 and 5-HT2A receptors. Bioorg Med Chem Lett 1998, 8, 24, 3571.

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)	22761	3,5-dimethoxybenzoic acid	1132-21-4	C₉H₁₀O₄	详情	详情
(II)	25566	(3,5-dimethoxy-2,5-cyclohexadien-1-yl)methanol		C₉H₁₄O₃	详情	详情
(III)	11818	Phenyl hydrazine; 1-Phenylhydrazine	100-63-0	C₆H₈N₂	详情	详情
(IV)	25567	2-(hydroxymethyl)-1,2,3,9-tetrahydro-4H-carbazol-4-one		C₁₃H₁₃NO₂	详情	详情
(V)	25568	(4-oxo-2,3,4,9-tetrahydro-1H-carbazol-2-yl)methyl 4-methylbenzenesulfonate		C₂₀H₁₉NO₄S	详情	详情
(VI)	17910	6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole		C₁₂H₁₃FN₂O	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

Acidic hydrolysis of the enol ether groups of 1,4-dihydro-3,5-dimethoxybenzyl alcohol (I) gave diketone (II). Subsequent condensation of (II) with chloroacetaldehyde in the presence of NaHCO3, followed by dehydration of the intermediate (III) upon acidic treatment, yielded the tetrahydrobenzofuranone (IV). Tosylate (V) was then prepared by reaction of alcohol (IV) with p-toluenesulfonyl chloride in cold pyridine. Finally, nucleophilic displacement of the tosylate group with benzisoxazolylpiperidine (VI) in N-methylpyrrolidone provided the title amine.

参考文献中间体

合成目标

【1】 Casariego, I.; et al.; New CNS agent precursors. A simple and efficient route for synthesis of 6-aminomethyl-4,5,6,7-tetrahydrobenzofuran-4-ones as conformationally constrained butyrophenone analogues. Tetrahedron Lett 1997, 38, 31, 5555.
【2】 Masaguer, C.F.; Casariego, I.; Raviña, E.; et al.; Conformationally constrained butyrophenones with affinity for dopamine (D1, D2, D4) and serotonin (5-HT2A, 5-HT2C) receptors: Synthesis of aminomethylbenzo[b]furanones and their evaluation as antipsychotics. J Med Chem 2000, 43, 24, 4678.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	25566	(3,5-dimethoxy-2,5-cyclohexadien-1-yl)methanol	C₉H₁₄O₃	详情	详情
(II)	47758	5-(hydroxymethyl)-1,3-cyclohexanedione	C₇H₁₀O₃	详情	详情
(III)	47759	2-[4-(hydroxymethyl)-2,6-dioxocyclohexyl]acetaldehyde	C₉H₁₂O₄	详情	详情
(IV)	47760	6-(hydroxymethyl)-6,7-dihydro-1-benzofuran-4(5H)-one	C₉H₁₀O₃	详情	详情
(V)	47761	(4-oxo-4,5,6,7-tetrahydro-1-benzofuran-6-yl)methyl 4-methylbenzenesulfonate	C₁₆H₁₆O₅S	详情	详情
(VI)	17910	6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole	C₁₂H₁₃FN₂O	详情	详情

Extended Information