(3R)-3-hydroxydecanoic acid -Drug Synthesis Database

【结构式】

【分子编号】64140

【品名】(3R)-3-hydroxydecanoic acid

【CA登记号】

【分子式】C₁₀H₂₀O₃

【分子量】188.267

【元素组成】C 63.8% H 10.71% O 25.49%

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：(II)

Saponification of (R)-methyl 3-hydroxydecanoate (I) gave hydroxy acid (II), which was reduced to diol (III) using LiAlH4. Selective sulfonylation of the primary hydroxyl group of (III) provided tosylate (IV). The secondary hydroxyl group of (IV) was subsequently alkylated with iodomethane in the presence of NaH to furnish the methyl ether (V).

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
(I)	59083	methyl (3R)-3-hydroxydecanoate	C₁₁H₂₂O₃	详情	详情
(II)	64140	(3R)-3-hydroxydecanoic acid	C₁₀H₂₀O₃	详情	详情
(III)	59084	(3R)-1,3-decanediol	C₁₀H₂₂O₂	详情	详情
(IV)	49121	(3R)-3-hydroxydecyl 4-methylbenzenesulfonate	C₁₇H₂₈O₄S	详情	详情
(V)	64141	(3R)-3-methoxydecyl 4-methylbenzenesulfonate	C₁₈H₃₀O₄S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Hydroxy acid (II) was converted to methyl ether (XLI) by treatment with trimethylsilyl diazomethane. Reduction of acid (XLI) to alcohol (XLII) was accomplished by treatment with DIBAL in cold dichloromethane. Alcohol (XLII) was transformed to alkyl iodide (XLIII) via tosylation to (V), followed by displacement of tosylate (V) with NaI in acetone. Alkylation of the known azido sugar (XLIV) with the alkyl iodide (XLIII) in the presence of Ag2O provided ether (XLV). Then, acidic acetonide (XLV) hydrolysis led to diol (XLVI). Selective alkylation of the primary hydroxyl group of (XLVI) using iodomethane in the presence of Ag2O, followed by reprotection of some desilylated product, furnished the methyl ether (XLVII). The secondary hydroxyl group of (XLVII) was then converted to phosphate ester (XLVIII) employing the same phosphitylation/oxidation sequence as above.

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
(II)	64140	(3R)-3-hydroxydecanoic acid	C₁₀H₂₀O₃	详情	详情
(V)	64141	(3R)-3-methoxydecyl 4-methylbenzenesulfonate	C₁₈H₃₀O₄S	详情	详情
(XLI)	64173	(3R)-3-methoxydecanoic acid	C₁₁H₂₂O₃	详情	详情
(XLII)	64174	(3R)-3-methoxy-1-decanol	C₁₁H₂₄O₂	详情	详情
(XLIII)	64175	(3R)-1-iodo-3-methoxydecane; (1R)-1-(2-iodoethyl)octyl methyl ether	C₁₁H₂₃IO	详情	详情
(XLIV)	59080	(4aR,6S,7R,8R,8aS)-7-azido-6-{[tert-butyl(dimethyl)silyl]oxy}-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-8-ol	C₁₅H₂₉N₃O₅Si	详情	详情
(XLV)	64176	[((4aR,6S,7R,8R,8aS)-7-azido-8-{[(3R)-3-methoxydecyl]oxy}-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-6-yl)oxy](tert-butyl)dimethylsilane; (4aR,6S,7R,8R,8aS)-7-azido-6-{[tert-butyl(dimethyl)silyl]oxy}-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-8-yl (3R)-3-methoxydecyl ether	C₂₆H₅₁N₃O₆Si	详情	详情
(XLVI)	64177	(2R,3S,4R,5R,6S)-5-azido-6-{[tert-butyl(dimethyl)silyl]oxy}-2-(hydroxymethyl)-4-{[(3R)-3-methoxydecyl]oxy}tetrahydro-2H-pyran-3-ol	C₂₃H₄₇N₃O₆Si	详情	详情
(XLVII)	64178	(2R,3S,4R,5R,6S)-5-azido-6-{[tert-butyl(dimethyl)silyl]oxy}-4-{[(3R)-3-methoxydecyl]oxy}-2-(methoxymethyl)tetrahydro-2H-pyran-3-ol	C₂₄H₄₉N₃O₆Si	详情	详情
(XLVIII)	64179	diallyl (2R,3S,4R,5R,6S)-5-azido-6-{[tert-butyl(dimethyl)silyl]oxy}-4-{[(3R)-3-methoxydecyl]oxy}-2-(methoxymethyl)tetrahydro-2H-pyran-3-yl phosphate	C₃₀H₅₈N₃O₉PSi	详情	详情

Extended Information