3-chloro-1-cyclopentene -Drug Synthesis Database

【结构式】

【分子编号】19541

【品名】3-chloro-1-cyclopentene

【CA登记号】

【分子式】C₅H₇Cl

【分子量】102.56328

【元素组成】C 58.55% H 6.88% Cl 34.57%

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)

The reaction of 5-methoxyheptyl chloride (I) with magnesium in THF gives the corresponding Grignard reagent (II), which is condensed with 3-chlorocyclopentene (III) in refluxing THF to yield 3-(5-methoxy-1-heptyl)cyclopentene (IV). The cyclization of (IV) with dichloroacetyl chloride (V) by means of triethylamine in refluxing hexane affords 2-(5-methoxy-1-heptyl)-6,6-dichlorobicyclo[3.2.0]heptan-7-one (VI), which is submitted to a ring expansion with diazometane in ether giving 2-(5-methoxy-1-heptyl-6,6-dichlorobicyclo[3.3.0]octan-7-one (VII). Finally, this compound is dechlorinated with Zn in acetic acid.

参考文献中间体

合成目标

【1】 Kasha, W.J. (CBD Corp.); Cycloaliphatic pharmaceutical cpds.. DE 3378265; EP 0107733; WO 8304019 .
【2】 Castaner, R.M.; Castaner, J.; Serradell, M.N.; Cyoctol. Drugs Fut 1987, 12, 11, 1012.

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)	19539	1-chloro-5-methoxyheptane; 5-chloro-1-ethylpentyl methyl ether		C₈H₁₇ClO	详情	详情
(II)	19540	chloro(5-methoxyheptyl)magnesium		C₈H₁₇ClMgO	详情	详情
(III)	19541	3-chloro-1-cyclopentene		C₅H₇Cl	详情	详情
(IV)	19542	5-(2-cyclopenten-1-yl)-1-ethylpentyl methyl ether; 3-(5-methoxyheptyl)-1-cyclopentene		C₁₃H₂₄O	详情	详情
(V)	17829	2,2-dichloroacetyl chloride; dichloroacetyl chloride	79-36-7	C₂HCl₃O	详情	详情
(VI)	19544	7,7-dichloro-4-(5-methoxyheptyl)bicyclo[3.2.0]heptan-6-one		C₁₅H₂₄Cl₂O₂	详情	详情
(VII)	19545	1,1-dichloro-4-(5-methoxyheptyl)hexahydro-2(1H)-pentalenone		C₁₆H₂₆Cl₂O₂	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 addition of HCl to cyclopentadiene (I) gives 3-chlorocyclopentene (II), which is converted to racemic 2-cyclopentene-1-carboxylic acid (III). Optical resolution of (II) by crystallization of its (-)-1-phenylethylamine yields the desired enantiomer (IV), which is reduced with LiAlH4 in ethyl ether affording the chiral carbinol (V) (ee 98%). The reaction of (V) successively with BuLi, CO2 and I2 provides the iodinated cyclic carbonate (VI), which is treated with DBU in hot toluene to give the unsaturated cyclic carbonate (VII). The condensation of (VII) with 2-amino-6-chloropurine (VIII) by means of a Pd catalyst yields the carbocyclic purine (IX), which is finally hydrolyzed with aqueous NaOH to afford the target carbocyclic guanine. Alternatively, carbinol (V) can also be obtained by the vitamin B12/Zn/NH4Cl-catalyzed isomerization of 1,2-epoxycyclopentane (X) to the chiral cyclopentenol (XI), which by a [2,3]-sigmatropic Wittig rearrangement with KH, ICH2-SnBu4 and BuLi yields the target carbinol (V). However, the enantiomeric excess obtained is only ee 54%.

参考文献中间体

合成目标

【1】 Hildbrand, S.; et al.; A short synthesis of (-)-carbovir. Helv Chim Acta 1994, 77, 5, 1236.

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)	11183	1,3-Cyclopentadiene		C₅H₆	详情	详情
(II)	19541	3-chloro-1-cyclopentene		C₅H₇Cl	详情	详情
(III)	45419	2-cyclopentene-1-carboxylic acid		C₆H₈O₂	详情	详情
(IV)	45420	(1S)-2-cyclopentene-1-carboxylic acid		C₆H₈O₂	详情	详情
(V)	45421	(1S)-2-cyclopenten-1-ylmethanol		C₆H₁₀O	详情	详情
(VI)	45422	(4aR,7S,7aS)-7-iodohexahydrocyclopenta[d][1,3]dioxin-2-one		C₇H₉IO₃	详情	详情
(VII)	17673	(4aR,7aR)-4,4a,5,7a-tetrahydrocyclopenta[d][1,3]dioxin-2-one		C₇H₈O₃	详情	详情
(VIII)	11644	6-Chloro-9H-purin-2-amine; 6-Chloro-9H-purin-2-ylamine; 2-Amino-6-chloropurine	10310-21-1	C₅H₄ClN₅	详情	详情
(IX)	45398	[(1S,4R)-4-(2-amino-6-chloro-9H-purin-9-yl)-2-cyclopenten-1-yl]methyl methyl carbonate		C₁₃H₁₄ClN₅O₃	详情	详情
(X)	38011	6-oxabicyclo[3.1.0]hexane	285-67-6	C₅H₈O	详情	详情
(XI)	45423	(1R)-2-cyclopenten-1-ol		C₅H₈O	详情	详情

Extended Information