3-oxotetradecanoic acid -Drug Synthesis Database

【结构式】

【分子编号】59107

【品名】3-oxotetradecanoic acid

【CA登记号】

【分子式】C₁₄H₂₆O₃

【分子量】242.35864

【元素组成】C 69.38% H 10.81% O 19.8%

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：(XLII)

Keto ester (XLI) was obtained by Reformatskii condensation of the organozinc reagent generated from benzyl bromoacetate (XL) with n-undecyl cyanide (XXXIX). Subsequent hydrogenolysis of the benzyl ester of (XLI) in the presence of Pearlman's catalyst furnished keto acid (XLII). Acylation of the diamino compound (XXXVIII) with ketoacid (XLII), by means of DCC, provided diamide (XLIII). Then, desilylation of (XLIII) to afford alcohol (XLIV) was accomplished employing HF in acetonitrile.

参考文献中间体

合成目标

【1】 Christ, W.J.; Kawata, T.; Hawkins, L.D.; Kobayashi, S.; Asano, O.; Rossignol, D.P. (Eisai Co., Ltd.); Anti-endotoxin cpds.. EP 0536969; JP 1993194470; US 5530113 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XXXVIII)	59104	(1R)-1-(2-{[(2R,3R,4R,5S,6R)-2-[((2R,3S,4R,5R,6S)-3-{[(allyloxy)carbonyl]oxy}-4-[((3R)-3-{[(allyloxy)carbonyl]oxy}decyl)oxy]-5-amino-6-{[tert-butyl(dimethyl)silyl]oxy}tetrahydro-2H-pyran-2-yl)methoxy]-3-amino-5-{[bis(allyloxy)phosphoryl]oxy}-6-(methoxymethyl)tetrahydro-2H-pyran-4-yl]oxy}ethyl)octyl (Z)-5-dodecenoate		C₆₅H₁₁₇N₂O₁₉PSi	详情	详情
(XXXIX)	59105	lauronitrile		C₁₂H₂₃N	详情	详情
(XL)	12869	benzyl 2-bromoacetate	5437-45-6	C₉H₉BrO₂	详情	详情
(XLI)	59106	benzyl 3-oxotetradecanoate		C₂₁H₃₂O₃	详情	详情
(XLII)	59107	3-oxotetradecanoic acid		C₁₄H₂₆O₃	详情	详情
(XLIII)	59108	(1R)-1-[2-({(2R,3R,4R,5S,6R)-2-({(2R,3S,4R,5R,6S)-3-{[(allyloxy)carbonyl]oxy}-4-[((3R)-3-{[(allyloxy)carbonyl]oxy}decyl)oxy]-6-{[tert-butyl(dimethyl)silyl]oxy}-5-[(3-oxotetradecanoyl)amino]tetrahydro-2H-pyran-2-yl}methoxy)-5-{[bis(allyloxy)phosphoryl]oxy}-6-(methoxymethyl)-3-[(3-oxotetradecanoyl)amino]tetrahydro-2H-pyran-4-yl}oxy)ethyl]octyl (Z)-5-dodecenoate		C₉₃H₁₆₅N₂O₂₃PSi	详情	详情
(XLIV)	59109	(1R)-1-[2-({(2R,3R,4R,5S,6R)-2-({(2R,3S,4R,5R)-3-{[(allyloxy)carbonyl]oxy}-4-[((3R)-3-{[(allyloxy)carbonyl]oxy}decyl)oxy]-6-hydroxy-5-[(3-oxotetradecanoyl)amino]tetrahydro-2H-pyran-2-yl}methoxy)-5-{[bis(allyloxy)phosphoryl]oxy}-6-(methoxymethyl)-3-[(3-oxotetradecanoyl)amino]tetrahydro-2H-pyran-4-yl}oxy)ethyl]octyl (Z)-5-dodecenoate		C₈₇H₁₅₁N₂O₂₃P	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XXXI)

The other monosaccharide building block (XXXIII) was also synthesized from the common intermediate (XII). Alkylation of (XII) with mesylate (XXIII), prepared from 1-decanol (XXII), gave the decyl ether (XXIV). After acidic acetonide hydrolysis of (XXIV) to yield (XXV), removal of the trifluoroacetamide by means of potassium tert-butoxide, with concomitant O-allyl group isomerization, furnished (XXVI). Imine (XXVII) was then obtained by exchange reaction of amine (XXVI) with benzophenone imine at 45 C. After silylation of the primary hydroxyl of (XXVII) with tert-butyldimethylsilyl chloride affording(XXVIII), the secondary hydroxyl group was protected as the allyl carbonate (XXIX) by sequential treatment with phosgene and then with allyl alcohol. Imine (XXIX) hydrolysis, followed by coupling of the resultant amine (XXX) with 3-oxotetradecanoic acid (XXXI) led to keto amide (XXXII). Precursor (XXXIII) was then obtained by desilylation of (XXXII) with HF.

参考文献中间体

合成目标

【1】 Kobayashi, S.; Kawata, T.; Christ, W.J.; Rossignol, D.P. (Eisai Co., Ltd.); Substd. liposaccharides useful in the treatment and prevention of endotoxemia. US 5750664; WO 9639411 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XII)	57540	N-[(4aR,6S,7R,8R,8aS)-6-(allyloxy)-8-hydroxy-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-7-yl]-2,2,2-trifluoroacetamide		C₁₄H₂₀F₃NO₆	详情	详情
(XXII)	40729	1-decanol	112-30-1	C₁₀H₂₂O	详情	详情
(XXIII)	64156	decyl methanesulfonate		C₁₁H₂₄O₃S	详情	详情
(XXIV)	64157	N-[(4aR,7R,8R,8aS)-6-(allyloxy)-8-(decyloxy)-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-7-yl]-2,2,2-trifluoroacetamide		C₂₄H₄₀F₃NO₆	详情	详情
(XXV)	64158	N-[(3R,4R,5S,6R)-2-(allyloxy)-4-(decyloxy)-5-hydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl]-2,2,2-trifluoroacetamide		C₂₁H₃₆F₃NO₆	详情	详情
(XXVI)	64159	(2R,3S,4R,5R)-5-amino-4-(decyloxy)-2-(hydroxymethyl)-6-[(Z)-1-propenyloxy]tetrahydro-2H-pyran-3-ol		C₁₉H₃₇NO₅	详情	详情
(XXVII)	64160	(2R,3S,4R,5R)-4-(decyloxy)-5-[(diphenylmethylene)amino]-2-(hydroxymethyl)-6-[(Z)-1-propenyloxy]tetrahydro-2H-pyran-3-ol		C₃₂H₄₅NO₅	详情	详情
(XXVIII)	64151	2,2,2-trichloroethyl (3R,4R,5S,6R)-5-hydroxy-4-{[(3R)-3-methoxydecyl]oxy}-6-(methoxymethyl)-2-[(Z)-1-propenyloxy]tetrahydro-2H-pyran-3-ylcarbamate		C₂₄H₄₂Cl₃NO₈	详情	详情
(XXIX)	64162	allyl (2R,3S,4R,5R)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-(decyloxy)-5-[(diphenylmethylene)amino]-6-[(Z)-1-propenyloxy]tetrahydro-2H-pyran-3-yl carbonate		C₄₂H₆₃NO₇Si	详情	详情
(XXX)	64163	allyl (2R,3S,4R,5R)-5-amino-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-(decyloxy)-6-[(Z)-1-propenyloxy]tetrahydro-2H-pyran-3-yl carbonate		C₂₉H₅₅NO₇Si	详情	详情
(XXXI)	59107	3-oxotetradecanoic acid		C₁₄H₂₆O₃	详情	详情
(XXXII)	64164	allyl (2R,3S,4R,5R)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-(decyloxy)-5-[(3-oxotetradecanoyl)amino]-6-[(Z)-1-propenyloxy]tetrahydro-2H-pyran-3-yl carbonate		C₄₃H₇₉NO₉Si	详情	详情
(XXXIII)	64165	allyl (2R,3S,4R,5R)-4-(decyloxy)-2-(hydroxymethyl)-5-[(3-oxotetradecanoyl)amino]-6-[(Z)-1-propenyloxy]tetrahydro-2H-pyran-3-yl carbonate		C₃₇H₆₅NO₉	详情	详情

合成路线3

该中间体在本合成路线中的序号：(XXXI)

Reduction of the azido group of disaccharide (LVII), followed by acylation of the resultant amine (LVIII) with keto acid (XXXI) produced keto amide (LIX). The Troc protecting group of (LIX) was then removed by reductive treatment with zinc-copper couple in AcOH yielding amine (LX).

参考文献中间体

合成目标

【1】 Kobayashi, S.; Kawata, T.; Christ, W.J.; Rossignol, D.P. (Eisai Co., Ltd.); Substd. liposaccharides useful in the treatment and prevention of endotoxemia. US 5750664; WO 9639411 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XXXI)	59107	3-oxotetradecanoic acid	C₁₄H₂₆O₃	详情	详情
(LVII)	64188	allyl (2R,3S,4R,5R)-5-azido-2-{[((2R,3R,4R,5S,6R)-5-{[bis(allyloxy)phosphoryl]oxy}-4-{[(3R)-3-methoxydecyl]oxy}-6-(methoxymethyl)-3-{[(2,2,2-trichloroethoxy)carbonyl]amino}tetrahydro-2H-pyran-2-yl)oxy]methyl}-6-{[tert-butyl(dimethyl)silyl]oxy}-4-(decyloxy)tetrahydro-2H-pyran-3-yl carbonate	C₅₃H₉₄Cl₃N₄O₁₇PSi	详情	详情
(LVIII)	64189	allyl (2R,3S,4R,5R)-5-amino-2-{[((2R,3R,4R,5S,6R)-5-{[bis(allyloxy)phosphoryl]oxy}-4-{[(3R)-3-methoxydecyl]oxy}-6-(methoxymethyl)-3-{[(2,2,2-trichloroethoxy)carbonyl]amino}tetrahydro-2H-pyran-2-yl)oxy]methyl}-6-{[tert-butyl(dimethyl)silyl]oxy}-4-(decyloxy)tetrahydro-2H-pyran-3-yl carbonate	C₅₃H₉₆Cl₃N₂O₁₇PSi	详情	详情
(LIX)	64190	allyl (2R,3S,4R,5R)-2-{[((2R,3R,4R,5S,6R)-5-{[bis(allyloxy)phosphoryl]oxy}-4-{[(3R)-3-methoxydecyl]oxy}-6-(methoxymethyl)-3-{[(2,2,2-trichloroethoxy)carbonyl]amino}tetrahydro-2H-pyran-2-yl)oxy]methyl}-6-{[tert-butyl(dimethyl)silyl]oxy}-4-(decyloxy)-5-[(3-oxotetradecanoyl)amino]tetrahydro-2H-pyran-3-yl carbonate	C₆₇H₁₂₀Cl₃N₂O₁₉PSi	详情	详情
(LX)	64191	allyl (2R,3S,4R,5R)-2-({[(2R,3R,4R,5S,6R)-3-amino-5-{[bis(allyloxy)phosphoryl]oxy}-4-{[(3R)-3-methoxydecyl]oxy}-6-(methoxymethyl)tetrahydro-2H-pyran-2-yl]oxy}methyl)-6-{[tert-butyl(dimethyl)silyl]oxy}-4-(decyloxy)-5-[(3-oxotetradecanoyl)amino]tetrahydro-2H-pyran-3-yl carbonate	C₆₄H₁₁₉N₂O₁₇PSi	详情	详情

Extended Information