methyl 7-oxoheptanoate -Drug Synthesis Database

【结构式】

【分子编号】21529

【品名】methyl 7-oxoheptanoate

【CA登记号】35376-00-2

【分子式】C₈H₁₄O₃

【分子量】158.19736

【元素组成】C 60.74% H 8.92% O 30.34%

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：(VI)

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2

该中间体在本合成路线中的序号：(III)

The reaction of 3(R)-(tert-butyldimethylsilyloxy)-4(R)-methoxy-4(R)-methyl-1-(tributylstannyl)-1(E)-octene (II) with butyllithium, cuprous iodide and tributylphosphine gives an intermediate copper derivative which is condensed first with 4(R)-(tert-butyldimethylsilyloxy)-2-cyclopentenone (I) and then with methyl 6-formylhexanoate (III) to give the 7-hydroxy PGE1 derivative (IV). The dehydration of (IV) with mesyl chloride yields the unsaturated PGE compound (V), which is reduced with tributystannyl hydride and finally deprotected with acetic acid in THF. The starting products (I) and (II) are obtained as follows: 1) The oxidation of cyclopentadiene (VI) gives 2-cyclopentene-1,4-diol (VII), which is acetylated to the diacetate (VIII). Selective hydrolysis of (VIII) yields (1S, 4R)-4-hydroxy-2-cyclopentenyl acetate (IX), which is protected with tert-butyldimethylsilyl chloride to the protected acetate (X). Partial hydrolysis of (X) affords the semiprotected alcohol (XI), which is finally oxidized to the cyclopentenone (I).

参考文献中间体

合成目标

【1】 Kolb, M.; Van Hijfte, L.; Ireland, R.E.; A highly convergent synthesis of mexiprostil: 16(R) 16-methoxy 16-methyl PGE1 methyl ester. Tetrahedron Lett 1988, 29, 51, 6769.

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)	13805	(4R)-4-[[tert-Butyl(dimethyl)silyl]oxy]-2-cyclopenten-1-one		C₁₁H₂₀O₂Si	详情	详情
(II)	21528	(1R,2R,3E)-1-butyl-2-[[tert-butyl(dimethyl)silyl]oxy]-1-methyl-4-(tributylstannyl)-3-butenyl methyl ether		C₂₈H₆₀O₂SiSn	详情	详情
(III)	21529	methyl 7-oxoheptanoate	35376-00-2	C₈H₁₄O₃	详情	详情
(IV)	21530	methyl 7-[(2R,3R)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-((E,3R,4R)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methoxy-4-methyl-1-octenyl)-5-oxocyclopentyl]-7-hydroxyheptanoate		C₃₅H₆₈O₇Si₂	详情	详情
(V)	21531	methyl 7-[(2R,3R)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-((E,3R,4R)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-methoxy-4-methyl-1-octenyl)-5-oxocyclopentylidene]heptanoate		C₃₅H₆₆O₆Si₂	详情	详情
(VI)	11183	1,3-Cyclopentadiene		C₅H₆	详情	详情
(VII)	21533	4-cyclopentene-1,3-diol		C₅H₈O₂	详情	详情
(VIII)	21534	4-(acetoxy)-2-cyclopenten-1-yl acetate		C₉H₁₂O₄	详情	详情
(IX)	21535	(1R,4R)-4-hydroxy-2-cyclopenten-1-yl acetate		C₇H₁₀O₃	详情	详情
(X)	21536	(1R,4R)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-cyclopenten-1-yl acetate		C₁₃H₂₄O₃Si	详情	详情
(XI)	21537	(1R,4R)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-cyclopenten-1-ol		C₁₁H₂₂O₂Si	详情	详情

Extended Information