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【结 构 式】 
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【分子编号】18810 【品名】(2R)-4,4,4-trifluoro-2-hydroxy-2-methyl-1-[4-(methylsulfanyl)phenyl]-1-butanone 【CA登记号】 |
【 分 子 式 】C12H13F3O2S 【 分 子 量 】278.2952296 【元素组成】C 51.79% H 4.71% F 20.48% O 11.5% S 11.52% |
合成路线1
该中间体在本合成路线中的序号：(VI)Alkylation of 2-(S)-tert-butyl-5-(S)-methyl-1,3-dioxolan-4-one (I) with 1,1,1-trifluoro-2-iodoethane (II) in the presence of LDA in THF at -72 C provided trifluoroethyl compound (III). Condensation of (III) with 4-(methylthio)phenyllithium (IV), prepared from 4-bromothioanisole and BuLi, gave (V), which was hydrolyzed with p-toluenesulfonic acid in boiling water to afford ketone (VI). Subsequent oxidation of sulfide group with KHSO5 (Oxone(R)) in the presence of Oct3NMeCl (Aliquat 336(R)) produced sulfone (VII). Esterification of (VII) with chloroacetic acid using 1-cyclohexyl-3-(2-morpholinoethyl)carbodiimide methyl-p-toluenesulfonate (CMC) as the condensing agent provided chloroacetate (VIII). Finally, condensation with 3,4-difluorophenol (IX) in the presence of DBU in acetonitrile gave the intermediate ether (X), which cyclized to produce the target furanone.
| 【1】 Belley, M.; Gauthier, J.Y.; Grimm, E.; Leblanc, Y.; Li, C.-S.; Therien, M.; Lau, C.-K.; Prasit, P.; Roy, P. (Merck Frosst Canada Inc.); (Methylsulfonyl)phenyl-2-(5H)-furanones as COX-2 inhibitors. EP 0863891; JP 1999500146; US 5981576; WO 9714691 . |
| 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) | 18805 | (2S,5S)-2-(tert-butyl)-5-methyl-1,3-dioxolan-4-one | C8H14O3 | 详情 | 详情 | |
| (II) | 18806 | 1,1,1-trifluoro-2-iodoethane | 353-83-3 | C2H2F3I | 详情 | 详情 |
| (III) | 18807 | (2S,5R)-2-(tert-butyl)-5-methyl-5-(2,2,2-trifluoroethyl)-1,3-dioxolan-4-one | C10H15F3O3 | 详情 | 详情 | |
| (IV) | 18808 | [4-(methylsulfanyl)phenyl]lithium | C7H7LiS | 详情 | 详情 | |
| (V) | 18809 | (2S,5R)-2-(tert-butyl)-5-methyl-4-[4-(methylsulfanyl)phenyl]-5-(2,2,2-trifluoroethyl)-1,3-dioxolan-4-ol | C17H23F3O3S | 详情 | 详情 | |
| (VI) | 18810 | (2R)-4,4,4-trifluoro-2-hydroxy-2-methyl-1-[4-(methylsulfanyl)phenyl]-1-butanone | C12H13F3O2S | 详情 | 详情 | |
| (VII) | 18811 | (2R)-4,4,4-trifluoro-2-hydroxy-2-methyl-1-[4-(methylsulfonyl)phenyl]-1-butanone | C12H13F3O4S | 详情 | 详情 | |
| (VIII) | 18812 | (1R)-3,3,3-trifluoro-1-methyl-1-[4-(methylsulfonyl)benzoyl]propyl 2-chloroacetate | C14H14ClF3O5S | 详情 | 详情 | |
| (IX) | 16739 | 3,4-difluorophenol | 2713-33-9 | C6H4F2O | 详情 | 详情 |
| (X) | 18814 | (1R)-3,3,3-trifluoro-1-methyl-1-[4-(methylsulfonyl)benzoyl]propyl 2-(3,4-difluorophenoxy)acetate | C20H17F5O6S | 详情 | 详情 |