7-[(1R,2S)-2-hexyl-5-oxocyclopentyl]heptanoic acid -Drug Synthesis Database

【结构式】

【分子编号】23958

【品名】7-[(1R,2S)-2-hexyl-5-oxocyclopentyl]heptanoic acid

【CA登记号】

【分子式】C₁₈H₃₂O₃

【分子量】296.45028

【元素组成】C 72.93% H 10.88% O 16.19%

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：(V)

The reaction of ricinoleic acid (I) with mercuric acetate - NaOH in THF - water gives 9,12 dihydroxyoctadecanoic acid (II), which by oxidation with CrO3 in H2SO4-water affords 9,12-dioxooctadecanoic acid (III) The cyclization of (III) with NaOH in refluxing ethanol-water yields 9-oxo-19,20-dinor-8(12)-prostenoic acid (IV), which is hydrogenated with H2 over PtO2 in acetic acid to give 9-oxo-19,20-dinorprostanoic acid (V). Finally, this compound is reduced again with NaBH4 in methanol, and treated with NaOH.

参考文献中间体

合成目标

【1】 Valcavi, U.; et al.; Synthesis of some derivatives of 19,20-dinorprostanoic acid. Farm Sci Ed 1975, 30, 7, 527.
【2】 Valcavi, U. (Dr. Madaus; Istituto Biochimico Italiano Giovanni Lorenzini SpA); 19,20-Bis-nor-prostanoic acids, process for their preparation and pharmaceutical compsns. containing them. DE 2535343 .
【3】 Castaner, J.; Prous, J.; Rosaprostol sodium. Drugs Fut 1986, 11, 8, 666.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	23955	Ricinoleic acid; (Z)-12-hydroxy-9-octadecenoic acid	C₁₈H₃₄O₃	详情	详情
(II)	23963	9,12-dihydroxyoctadecanoic acid	C₁₈H₃₆O₄	详情	详情
(III)	23956	9,12-dioxooctadecanoic acid	C₁₈H₃₂O₄	详情	详情
(IV)	23957	7-(2-hexyl-5-oxo-1-cyclopenten-1-yl)heptanoic acid	C₁₈H₃₀O₃	详情	详情
(V)	23958	7-[(1R,2S)-2-hexyl-5-oxocyclopentyl]heptanoic acid	C₁₈H₃₂O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IX)

A new synthesis of racemic rosaprostol has been reported: The condensation of methyl decanoate (I) with dimethyl methylphosphonate (II) by means of butyllithium in THF gives dimethyl 2-oxoundecylphosphonate (III), which is treated with tosyl azide and NaH in benzene/THF yielding the alpha-diazo compound (IV). The cyclization of (IV) by means of rhodium acetate in refluxing dichloromethane affords trans-2-(dimethoxyphosphoryl)-3-hexylcyclopentanone (V), which is condensed with methyl 6-formylhexanoate (VI) by means of NaOH/Al2O3 in benzene giving methyl 6-(2-hexyl-5-oxocyclopentylidene)hexanoate (VII). The selective reduction of (VII) with sodium tellurohydride (NaHTe) in ethanol gives the saturated ester (VIII), which is hydrolyzed with NaOH in hot ethanol yielding the corresponding free acid (IX). Finally, this compound is reduced to the target compound with NaBH4 in methanol.

参考文献中间体

合成目标

【1】 Mikolajczyk, M.; Zurawinski, R.; Synthesis of (±)-rosaprostol. J Org Chem 1998, 63, 24, 8894.

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)	26017	methyl decanoate	110-42-9	C₁₁H₂₂O₂	详情	详情
(II)	13607	dimethyl methylphosphonate	756-79-6	C₃H₉O₃P	详情	详情
(III)	26018	dimethyl 2-oxoundecylphosphonate		C₁₃H₂₇O₄P	详情	详情
(IV)	26019	dimethyl 1-diazo-2-oxoundecylphosphonate		C₁₃H₂₅N₂O₄P	详情	详情
(V)	26020	dimethyl (1S,2R)-2-hexyl-5-oxocyclopentylphosphonate		C₁₃H₂₅O₄P	详情	详情
(VI)	21529	methyl 7-oxoheptanoate	35376-00-2	C₈H₁₄O₃	详情	详情
(VII)	26021	methyl 7-(2-hexyl-5-oxocyclopentylidene)heptanoate		C₁₉H₃₂O₃	详情	详情
(VIII)	26022	methyl 7-[(1R,2S)-2-hexyl-5-oxocyclopentyl]heptanoate		C₁₉H₃₄O₃	详情	详情
(IX)	23958	7-[(1R,2S)-2-hexyl-5-oxocyclopentyl]heptanoic acid		C₁₈H₃₂O₃	详情	详情

合成路线3

该中间体在本合成路线中的序号：(VIII)

A new synthesis of rosaprostol has been developed: Reaction of 3-(dimethoxyphosphorylmethyl)-2-cyclopenten-1-one (I) with 7-iodoheptanoic acid methyl ester (II) by means of NaH in DMSO gives the C-2 alkylated cyclopentenone (III), which is condensed with pentanal (IV) by means of NaOMe in methanol to yield the dienone (V). Reduction of the double bonds of (V) with H2 over PtO2 in acetic acid affords a mixture of the cis- and trans-cyclopentanones (VI) and (VII) which, without isolation, is submitted to epimerization with TsOH in methanol to furnish almost quantitatively the desired trans-isomer (VII). The hydrolysis of the methyl ester of (VII) with NaOH in dioxane/water gives the corresponding carboxylic acid (VIII), which is finally hydrogenated with NaBH4 in methanol.

参考文献中间体

合成目标

【1】 Jankowiak, A.; Mikina, M.; Mikoajczyk, M.; Mphaphlele, M.J.; A new synthesis of racemic rosaprostol. Synthesis 2000, 8, 1075.

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)	48222	dimethyl (3-oxo-1-cyclopenten-1-yl)methylphosphonate		C₈H₁₃O₄P	详情	详情
(II)	48223	methyl 7-iodoheptanoate		C₈H₁₅IO₂	详情	详情
(III)	48224	methyl 7-[2-[(dimethoxyphosphoryl)methyl]-5-oxo-1-cyclopenten-1-yl]heptanoate		C₁₆H₂₇O₆P	详情	详情
(IV)	13409	n-Valeraldehyde; Pentanal	110-62-3	C₅H₁₀O	详情	详情
(V)	48225	methyl 7-[2-[(E)-1-hexenyl]-5-oxo-1-cyclopenten-1-yl]heptanoate		C₁₉H₃₀O₃	详情	详情
(VI)	48226	methyl 7-[(1R,2R)-2-hexyl-5-oxocyclopentyl]heptanoate		C₁₉H₃₄O₃	详情	详情
(VII)	48227	methyl 7-[(1S,2R)-2-hexyl-5-oxocyclopentyl]heptanoate		C₁₉H₃₄O₃	详情	详情
(VIII)	23958	7-[(1R,2S)-2-hexyl-5-oxocyclopentyl]heptanoic acid		C₁₈H₃₂O₃	详情	详情

Extended Information