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【结 构 式】 
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【分子编号】28681 【品名】(3R)-4,4,4-trifluoro-3-hydroxybutyl 4-methylbenzenesulfonate 【CA登记号】 |
【 分 子 式 】C11H13F3O4S 【 分 子 量 】298.2830296 【元素组成】C 44.29% H 4.39% F 19.11% O 21.46% S 10.75% |
合成路线1
该中间体在本合成路线中的序号：(I)Befloxatone is obtained by condensation of 1,1,1-trifluoro-4-(tosyloxy)-2(R)-butanol (I) with 3-(4-hydroxyphenyl)-5(R)-(methoxymethyl)oxazolidin-2-one (II) by means of K2CO3 in hot DMF.
| 【1】 Castaner, J.; Sorbera, L.A.; Rabasseda, X.; Befloxatone. Drugs Fut 1999, 24, 10, 1057. |
| 【2】 Koenig, J.-J.; Schoofs, A.; Jarreau, F.-X.; Rovei, V. (Laboratoires Delalande); 3-Aryl oxazolidinones, process for their preparation and their therapeutical use. EP 0424243; EP 0424244; EP 0428421; JP 1992502333; JP 1992502334; JP 1992502335; US 5036090; US 5036091; US 5171747; US 5196543; WO 9105775 . |
| 【3】 Jarreau, F.-X.; Koenig, J.-J.; Rovei, V. (Laboratoires Delalande); 3-Aryl-oxazolidinone derivs., process for their preparation and their use in therapeutics. EP 0511031; FR 2675504; JP 1993112542; US 5264443 . |
合成路线2
该中间体在本合成路线中的序号：(I)1) Synthesis of Butanol (I): 1a) The reduction of 4,4,4-trifluoro-2-oxobutyric acid ethyl ester (III) with NaBH4 in dichloromethane gives 4,4,4-trifluoro-2-hydroxybutyric acid ethyl ester (IV), which is hydrolyzed with NaOH in ethanol, yielding the corresponding acid (V). The optical resolution of (V) with 1(S)-phenylethylamine in hot ethanol affords the 3(R)-hydroxy enantiomer (VI) (1,3), which is reduced with NaBH4 and BF3 ethearate in THF to provide 4,4,4-trifluorobutane-1,3(R)-diol (VII). Finally, this compound is monotosylated by means of tosyl chloride and DMAP in pyridine to afford intermediate (I). 1b) The digestion of 4,4,4-trifluoro-3-hydroxybutyric acid ethyl ester (IV) with Novozym in a phosphate buffer gives the corresponding (R)-enantiomer (VIII), which is reduced with NaBH4 in ethanol, yielding 4,4,4-trifluorobutane-1,3(R)-diol (VII) (4). Finally, this compound is monotosylated by means of tosyl chloride as before to give butanol (I).
| 【1】 Castaner, J.; Sorbera, L.A.; Rabasseda, X.; Befloxatone. Drugs Fut 1999, 24, 10, 1057. |
| 【2】 Koenig, J.-J.; Schoofs, A.; Jarreau, F.-X.; Rovei, V. (Laboratoires Delalande); 3-Aryl oxazolidinones, process for their preparation and their therapeutical use. EP 0424243; EP 0424244; EP 0428421; JP 1992502333; JP 1992502334; JP 1992502335; US 5036090; US 5036091; US 5171747; US 5196543; WO 9105775 . |
| 【3】 Jarreau, F.-X.; Koenig, J.-J.; Rovei, V. (Laboratoires Delalande); 3-Aryl-oxazolidinone derivs., process for their preparation and their use in therapeutics. EP 0511031; FR 2675504; JP 1993112542; US 5264443 . |
| 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) | 28681 | (3R)-4,4,4-trifluoro-3-hydroxybutyl 4-methylbenzenesulfonate | C11H13F3O4S | 详情 | 详情 | |
| (III) | 25432 | ethyl 4,4,4-trifluoro-3-oxobutanoate | 372-31-6 | C6H7F3O3 | 详情 | 详情 |
| (IV) | 28683 | ethyl 4,4,4-trifluoro-3-hydroxybutanoate | 372-30-5 | C6H9F3O3 | 详情 | 详情 |
| (V) | 28684 | 4,4,4-trifluoro-3-hydroxybutyric acid | C4H5F3O3 | 详情 | 详情 | |
| (VI) | 28685 | (3R)-4,4,4-trifluoro-3-hydroxybutyric acid | C4H5F3O3 | 详情 | 详情 | |
| (VII) | 28686 | (3R)-4,4,4-trifluoro-1,3-butanediol | C4H7F3O2 | 详情 | 详情 | |
| (VIII) | 28687 | (3R)-4,4,4-Trifluoro-3-hydroxybutanoic acid ethyl ester | 85571-85-3 | C6H9F3O3 | 详情 | 详情 |