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【结 构 式】 
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【分子编号】19265 【品名】methyl 4-(2-phenylethynyl)phenyl sulfone; methyl(dioxo)[4-(2-phenylethynyl)phenyl]-lambda(6)-sulfane 【CA登记号】 |
【 分 子 式 】C15H12O2S 【 分 子 量 】256.32508 【元素组成】C 70.29% H 4.72% O 12.48% S 12.51% |
合成路线1
该中间体在本合成路线中的序号：(XIII)4) The oxidation of 4-(methylsulfanyl)acetophenone (X) with monoperoxyphthalic acid (MMPP) in dichloro-methane/methanol gives the corresponding sulfone (XI), which is brominated with Br2/AlCl3 in chloroform, yielding the expected phenacyl bromide (XII). Finally, this compound is cyclocondensed with phenylacetic acid (I) by means of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and triethylamine in acetonitrile. 5) Reaction of [4-(methylsulfonyl)phenyl]phenylacetyl-ene (XIII) with CO catalyzed by Rh4(CO)12 in THF at 100 C in a stainless steel autoclave at 100 Atm pressure, followed by a chromatographic separation in a silicagel column to eliminate the undesired regioisomer.
| 【1】 Sorbera, L.A.; Rabasseda, X.; Castañer, J.; Rofecoxib. Drugs Fut 1998, 23, 12, 1287. |
| 【2】 Atkinson, J.G.; Wang, Z. (Merck Frosst Canada Inc.); Stilbene derivs. useful as cyclooxygenase-2 inhibitors. EP 0788476; JP 1998507765; WO 9613483 . |
| 【3】 Ducharme, Y.; Gauthier, J.Y.; Prasit, P.; Leblanc, Y.; Wang, Z.; Leger, S.; Therien, M. (Merck Frosst Canada Inc.); Phenyl heterocycles as cyclooxygenase-2 inhibitors. EP 0705254; EP 0739340; EP 0754687; EP 0822190; EP 0980866; JP 1997500372; JP 1997506631; JP 2000038375; US 5474995; WO 9500501; WO 9518799 . |
| 【4】 Hancock, B.; Winters, C.; Gertz, B.; Ehrich, E. (Merck & Co., Inc.; Merck Frosst Canada Inc.); Compsns. for a once a day treatment of cyclooxygenase-2 mediated diseases. JP 1999512754; WO 9744028 . |
| 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) | 16148 | Benzeneacetic acid; 2-Phenylacetic acid; Phenyl Acetic Acid | 103-82-2 | C8H8O2 | 详情 | 详情 |
| (X) | 19262 | 1-[4-(methylsulfanyl)phenyl]-1-ethanone；4'-Methylthioacetophenon；4’-(methylthio)acetophenone | 1778-09-2 | C9H10OS | 详情 | 详情 |
| (XI) | 19263 | 1-[4-(methylsulfonyl)phenyl]-1-ethanone; 4-methylsulfonylacetophenone | 10297-73-1 | C9H10O3S | 详情 | 详情 |
| (XII) | 19264 | 2-bromo-1-[4-(methylsulfonyl)phenyl]-1-ethanone | C9H9BrO3S | 详情 | 详情 | |
| (XIII) | 19265 | methyl 4-(2-phenylethynyl)phenyl sulfone; methyl(dioxo)[4-(2-phenylethynyl)phenyl]-lambda(6)-sulfane | C15H12O2S | 详情 | 详情 |