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【结 构 式】 
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【分子编号】39899 【品名】ethoxy(tetrahydro-4H-pyran-4-ylidene)methyl trimethylsilyl ether; [ethoxy(tetrahydro-4H-pyran-4-ylidene)methoxy](trimethyl)silane 【CA登记号】 |
【 分 子 式 】C11H22O3Si 【 分 子 量 】230.37938 【元素组成】C 57.35% H 9.63% O 20.83% Si 12.19% |
合成路线1
该中间体在本合成路线中的序号：(VI)The sulfonation of 4-chlorodiphenyl ether (I) with chlorosulfonic acid in dichloromethane gives the 4-(4-chlorophenoxy)benzenesulfonic acid (II), which is treated with oxalyl chloride and DMF in the same solvent yielding the sulfonyl chloride (III). The reduction of (III) with trimethyl phosphite and KOH in toluene affords the methylsulfanyl derivative (IV), which is chlorinated with SO2Cl2 in dichloromethane to give the chloromethylsulfanyl derivative (V). The condensation of (V) with the silylated enol ether (VI) by means of ZnCl2 and KOH in refluxing dichloromethane yields 4-[4-(4-chlorophenoxy)phenylsulfanylmethyl]tetrahydropyran-4-carboxylic acid (VII), which is treated with oxalyl chloride affording the corresponding acyl chloride (VIII). The reaction of (VIII) with NH2OH in dichloromethane provides the carbohydroxamic acid (IX), which is finally oxidized with oxone (potassium peroxymonosulfate) in N-methyl-2-pyrrolidone/H2O to furnish the target sulfone.
| 【1】 Zook, S.E.; Dagnino, R. Jr.; Deason, M.E.; Bender, S.L.; Melnick, M.J. (Agouron Pharmaceuticals, Inc.); Metalloproteinase inhibitors, pharmaceutical compsns. containing them and their pharmaceutical uses, and methods and intermediates useful for their preparation. EP 0874830; JP 2000502330; WO 9720824 . |
| 【2】 Campbell, J.A.; Dvorak, C.A.; Fisher, L.E.; McGrane, P.L. (F. Hoffmann-La Roche AG); Process for preparing 3-arylsulfur hydroxamic acids. EP 0965592 . |
| 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) | 39894 | 1-chloro-4-phenoxybenzene; 4-chlorophenyl phenyl ether | 7005-72-3 | C12H9ClO | 详情 | 详情 |
| (II) | 39895 | 4-(4-chlorophenoxy)benzenesulfonic acid | C12H9ClO4S | 详情 | 详情 | |
| (III) | 39896 | 4-(4-chlorophenoxy)benzenesulfonyl chloride | C12H8Cl2O3S | 详情 | 详情 | |
| (IV) | 39897 | 4-chlorophenyl 4-(methylsulfanyl)phenyl ether; 1-(4-chlorophenoxy)-4-(methylsulfanyl)benzene | 225652-11-9 | C13H11ClOS | 详情 | 详情 |
| (V) | 39898 | 1-[(chloromethyl)sulfanyl]-4-(4-chlorophenoxy)benzene; 4-[(chloromethyl)sulfanyl]phenyl 4-chlorophenyl ether | C13H10Cl2OS | 详情 | 详情 | |
| (VI) | 39899 | ethoxy(tetrahydro-4H-pyran-4-ylidene)methyl trimethylsilyl ether; [ethoxy(tetrahydro-4H-pyran-4-ylidene)methoxy](trimethyl)silane | C11H22O3Si | 详情 | 详情 | |
| (VII) | 39900 | 4-([[4-(4-chlorophenoxy)phenyl]sulfanyl]methyl)tetrahydro-2H-pyran-4-carboxylic acid | C19H19ClO4S | 详情 | 详情 | |
| (VIII) | 39901 | 4-([[4-(4-chlorophenoxy)phenyl]sulfanyl]methyl)tetrahydro-2H-pyran-4-carbonyl chloride | C19H18Cl2O3S | 详情 | 详情 | |
| (IX) | 39902 | 4-([[4-(4-chlorophenoxy)phenyl]sulfanyl]methyl)-N-hydroxytetrahydro-2H-pyran-4-carboxamide | C19H20ClNO4S | 详情 | 详情 | |
| (X) | 16829 | Diethyl malonate | 105-53-3 | C7H12O4 | 详情 | 详情 |
| (XI) | 12060 | Bis(2-chloroethyl) ether; 1-Chloro-2-(2-chloroethoxy)ethane; 2,2'-Dichlorodiethyl ether | 111-44-4 | C4H8Cl2O | 详情 | 详情 |
| (XII) | 18726 | diethyl tetrahydro-4H-pyran-4,4-dicarboxylate | C11H18O5 | 详情 | 详情 | |
| (XIII) | 39003 | N-butyl-2-cyclohexylacetamide | C12H23NO | 详情 | 详情 |