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【结 构 式】

【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%

与该中间体有关的原料药合成路线共 1 条

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
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