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【结 构 式】 
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【分子编号】36576 【品名】1,1-dimethyl-2-[4-(methylsulfonyl)phenyl]-2-oxoethyl 2-chloroacetate 【CA登记号】 |
【 分 子 式 】C13H15ClO5S 【 分 子 量 】318.7778 【元素组成】C 48.98% H 4.74% Cl 11.12% O 25.09% S 10.06% |
合成路线1
该中间体在本合成路线中的序号：(VII)Friedel-Crafts acylation of thioanisole (I) with isobutyryl chloride (II) in the presence of AlCl3 gave ketone (III), which was hydroxylated with NaOH and a phase-transfer agent in CCl4-toluene to provide hydroxyketone (IV). Subsequent oxidation of the sulfide group employing Oxone(tm) gave rise to sulfone (V) (1). Further esterification of (V) with chloroacetyl chloride (VI) and pyridine yielded chloroacetate ester (VII), which was cyclized to the epoxy lactone (VIII) by treatment with DBU in acetonitrile. Finally, epoxide opening with the potassium salt of 5-bromo-2-hydroxypyridine (IX) produced the title (pyridyloxy)furanone.
| 【1】 Chan, C.C.; Lau, C.K.; Brideau, C.; et al.; Synthesis and biological evaluation of 3-heteroaryloxy-4-phenyl-2(5H)-furanones as selective COX-2 inhibitors. Bioorg Med Chem Lett 1999, 9, 22, 3187. |
| 【2】 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) | 19272 | methyl phenyl sulfide; 1-(methylsulfanyl)benzene | 100-68-5 | C7H8S | 详情 | 详情 |
| (II) | 14932 | isobutyryl chloride; 2-methylpropanoyl chloride | 79-30-1 | C4H7ClO | 详情 | 详情 |
| (III) | 36573 | 2-methyl-1-[4-(methylsulfanyl)phenyl]-1-propanone | C11H14OS | 详情 | 详情 | |
| (IV) | 36574 | 2-hydroxy-2-methyl-1-[4-(methylsulfanyl)phenyl]-1-propanone | C11H14O2S | 详情 | 详情 | |
| (V) | 36575 | 2-hydroxy-2-methyl-1-[4-(methylsulfonyl)phenyl]-1-propanone | C11H14O4S | 详情 | 详情 | |
| (VI) | 11296 | 2-Chloroacetyl chloride; Chloroacetic chloride | 79-04-9 | C2H2Cl2O | 详情 | 详情 |
| (VII) | 36576 | 1,1-dimethyl-2-[4-(methylsulfonyl)phenyl]-2-oxoethyl 2-chloroacetate | C13H15ClO5S | 详情 | 详情 | |
| (VIII) | 36577 | 4,4-dimethyl-5-[4-(methylsulfonyl)phenyl]-3,6-dioxabicyclo[3.1.0]hexan-2-one | C13H14O5S | 详情 | 详情 | |
| (IX) | 36578 | potassium 5-bromo-2-pyridinolate | C5H3BrKNO | 详情 | 详情 |