【结 构 式】 |
【分子编号】13091 【品名】(3R)-1-Methyl-3-[[(4-methylphenyl)sulfonyl]oxy]tetrahydrothiophenium 【CA登记号】 |
【 分 子 式 】C12H17O3S2 【 分 子 量 】273.39718 【元素组成】C 52.72% H 6.27% O 17.56% S 23.46% |
合成路线1
该中间体在本合成路线中的序号:(XXII)2) The intermediate 3(R)-(p-toluenesulfonyloxy)thiolane (VII) can be obtained by two other synthetic pathways: a) The racemic 2-hydroxy-4-(methylsulfanyl)butyric acid ethyl ester (XVIII) is submitted to optical resolution with Pseudomonas fluorescens lipase in toluene/water, yielding the corresponding 2(R)-hydroxy ester (XIX), which is reduced with NaBH4 in THF/water to afford 4-(methylsulfanyl)butane-1,2(R)-diol (XX). The acylation of (XX) with p-toluenesulfonyl chloride and pyridine yields the ditosylate (XXI), which is cyclized in refluxing benzene to give 1(R)-methyl-3(R)-(p-toluenesulfonyloxy)thiolanium p-toluenesulfonate (XXII). Finally, this compound is treated with trifluoroacetic acid in pyridine to afford the thiolane (VII), already described. b) The reduction of 4-chloro-3(R)-hydroxybutyric acid methyl ester (XXIII) with lithium borohydride in THF gives 4-chlorobutane-1,3(R)-diol (XXIV), which is tosylated as before, yielding the bis(tosyloxy) derivative (XXV). Finally, this compound is cyclized with Na2S in hot acetonitrile/water to afford the thiolane (VII), already described.
【1】 Mealy, N.; Castaner, J.; Sulopenem. Drugs Fut 1996, 21, 7, 706. |
【2】 Urban, F.J.; Breitenbach, R.; Vincent, L.A.; Synthesis of optically active 3(R)-[(alkylsulfonyl)oxy]thiolanes from 2(R)-hydroxy-4-(methylthio)butanoic acid or D-methionine. J Org Chem 1990, 55, 11, 3670-2. |
【3】 Volkmann, R.A. (Pfizer Inc.); Process for optically active 3-thiolanyl sulfonate esters. US 4921972 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(XVIII) | 13087 | ethyl 2-hydroxy-4-(methylsulfanyl)butanoate | C7H14O3S | 详情 | 详情 | |
(XIX) | 13088 | ethyl (2R)-2-hydroxy-4-(methylsulfanyl)butanoate | C7H14O3S | 详情 | 详情 | |
(XX) | 13089 | (2R)-4-(Methylsulfanyl)-1,2-butanediol | C5H12O2S | 详情 | 详情 | |
(XXI) | 13090 | (2R)-2-[[(4-methylphenyl)sulfonyl]oxy]-4-(methylsulfanyl)butyl 4-methylbenzenesulfonate | C19H24O6S3 | 详情 | 详情 | |
(XXII) | 13091 | (3R)-1-Methyl-3-[[(4-methylphenyl)sulfonyl]oxy]tetrahydrothiophenium | C12H17O3S2 | 详情 | 详情 | |
(XXIII) | 13092 | methyl (3R)-4-chloro-3-hydroxybutanoate | C5H9ClO3 | 详情 | 详情 | |
(XXIV) | 13093 | (3R)-4-Chloro-1,3-butanediol | C4H9ClO2 | 详情 | 详情 | |
(XXV) | 13094 | (3R)-4-chloro-3-[[(4-methylphenyl)sulfonyl]oxy]butyl 4-methylbenzenesulfonate | C18H21ClO6S2 | 详情 | 详情 |