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【结 构 式】 
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【分子编号】52291 【品名】Cyclopropanone ethyl trimethylsilyl acetal; (1-Ethoxycyclopropoxy)trimethylsilane 【CA登记号】 |
【 分 子 式 】C8H18O2Si 【 分 子 量 】174.31522 【元素组成】C 55.12% H 10.41% O 18.36% Si 16.11% |
合成路线1
该中间体在本合成路线中的序号：(LXXVIII)The organozinc reagent (LXXIX) was prepared by treatment of [(1-ethoxycyclopropyl)oxy]trimethylsilane (LXXVIII) with ZnCl2. Palladium-catalyzed coupling of (LXXIX) to phthalimidoacetyl chloride (VIII) furnished ethyl phthalimodolevulinate (XLI), which was finally hydrolyzed as in precedent methods.
| 【1】 Wang, J.; Scott, A.I.; An efficient synthesis of delta-aminolevulinic acid (ALA) and its isotopomers. Tetrahedron Lett 1997, 38, 5, 739. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VIII) | 10278 | 2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)acetyl chloride | 6780-38-7 | C10H6ClNO3 | 详情 | 详情 |
| (XLI) | 59167 | ethyl 5-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-4-oxopentanoate | C15H15NO5 | 详情 | 详情 | |
| (LXXVIII) | 52291 | Cyclopropanone ethyl trimethylsilyl acetal; (1-Ethoxycyclopropoxy)trimethylsilane | C8H18O2Si | 详情 | 详情 | |
| (LXXIX) | 59200 | bis(3-ethoxy-3-oxopropyl)zinc | C10H18O4Zn | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VIII)Ethyl nipecotate (I) was protected as the tert-butyl carbamate (II) upon treatment with Boc2O in THF. The lithium enolate of ester (II) was then sulfenylated with the disulfide (IV), prepared by oxidation of 4-fluorothiophenol (III), yielding thioether (V). This was further oxidized to the corresponding sulfone (VI) using meta-chloroperbenzoic acid. Acid cleavage of the Boc protecting group of (VI) gave piperidine (VII), which was converted to the N-cyclopropyl amine (IX) by reductive alkylation with [(1-ethoxycyclopropyl)oxy]trimethylsilane (VIII) in the presence of NaBH3CN. Displacement of the aryl fluoride of (IX) with 4-(trifluoromethoxy)phenol (X) under basic conditions afforded the diaryl ether (XI). After saponification of the ester group of (XI), the resultant carboxylic acid (XII) was coupled to O-(tetrahydropyranyl)hydroxylamine by means of EDC to produce the protected hydroxamate (XIII). Finally, removal of the tetrahydropyranyl protecting group of (XIII) with HCl in dioxan afforded the title compound.
| 【1】 Villamil, C.I.; et al.; Design and synthesis of 4,4-disubstituted piperidine alpha-sulphone hydroxamates as potent and selective MMP inhibitors: The discovery of SC-77964. 222nd ACS Natl Meet (Aug 26 2001, Chicago) 2001, Abst MEDI 258. |
| 【2】 Aromatic sulfone hydroxamic acid metalloprotease inhibitor. WO 0050396 . |
| 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) | 17410 | Ethyl isonipecotate; ethyl 4-piperidinecarboxylate | 1126-09-6 | C8H15NO2 | 详情 | 详情 |
| (II) | 49847 | 1-(tert-butyl) 4-ethyl-1,4-piperidinedicarboxylate; N-Boc-4-Carbethoxypiperidine | 142851-03-4 | C13H23NO4 | 详情 | 详情 |
| (III) | 22971 | 4-fluorobenzenethiol; 4-fluorophenylhydrosulfide; 4-Fluorothiophenol | 371-42-6 | C6H5FS | 详情 | 详情 |
| (IV) | 52287 | bis(4-fluorophenyl) disulfide; 1-fluoro-4-[(4-fluorophenyl)disulfanyl]benzene | C12H8F2S2 | 详情 | 详情 | |
| (V) | 52288 | 1-(1,1-dimethylethyl) 4-ethyl 4-[(4-fluorophenyl)sulfanyl]-1,4-piperidinedicarboxylate | C19H26FNO4S | 详情 | 详情 | |
| (VI) | 52289 | 1-(1,1-dimethylethyl) 4-ethyl 4-[(4-fluorophenyl)sulfonyl]-1,4-piperidinedicarboxylate | C19H26FNO6S | 详情 | 详情 | |
| (VII) | 52290 | ethyl 4-[(4-fluorophenyl)sulfonyl]-4-piperidinecarboxylate | C14H18FNO4S | 详情 | 详情 | |
| (VIII) | 52291 | Cyclopropanone ethyl trimethylsilyl acetal; (1-Ethoxycyclopropoxy)trimethylsilane | C8H18O2Si | 详情 | 详情 | |
| (IX) | 52292 | ethyl 1-cyclopropyl-4-[(4-fluorophenyl)sulfonyl]-4-piperidinecarboxylate | C17H22FNO4S | 详情 | 详情 | |
| (X) | 18780 | 4-(trifluoromethoxy)phenol | 828-27-3 | C7H5F3O2 | 详情 | 详情 |
| (XI) | 52293 | ethyl 1-cyclopropyl-4-{[4-({4-[(trifluoromethyl)oxy]phenyl}oxy)phenyl]sulfonyl}-4-piperidinecarboxylate | C24H26F3NO6S | 详情 | 详情 | |
| (XII) | 52294 | 1-cyclopropyl-4-{[4-({4-[(trifluoromethyl)oxy]phenyl}oxy)phenyl]sulfonyl}-4-piperidinecarboxylic acid | C22H22F3NO6S | 详情 | 详情 | |
| (XIII) | 52295 | 1-cyclopropyl-N-(tetrahydro-2H-pyran-2-yloxy)-4-{[4-({4-[(trifluoromethyl)oxy]phenyl}oxy)phenyl]sulfonyl}-4-piperidinecarboxamide | C27H31F3N2O7S | 详情 | 详情 |