|
【结 构 式】 
|
【分子编号】56377 【品名】ethyl 4-[(4-fluorophenyl)sulfonyl]-1-(2-propynyl)-4-piperidinecarboxylate 【CA登记号】 |
【 分 子 式 】C17H20FNO4S 【 分 子 量 】353.4145432 【元素组成】C 57.78% H 5.7% F 5.38% N 3.96% O 18.11% S 9.07% |
合成路线1
该中间体在本合成路线中的序号：(IX)Ethyl isonipecotate (I) was protected as the N-Boc derivative (II) employing di-tert-butyl dicarbonate. Sulfenylation of the lithium enolate of ester (II) with the disulfide (IV), generated from the oxidation of 4-fluorothiophenol (III), furnished the phenylsulfanyl derivative (V). Thioether (V) was then oxidized to the corresponding sulfone (VI) by means of meta-chloroperbenzoic acid. After acidic Boc group cleavage in (VI), the resultant piperidine (VII) was alkylated with propargyl bromide (VIII) to produce the N-propargyl piperidine (IX).
| 【1】 Becker, D.P.; Hockerman, S.L.; Barta, T.E.; et al.; Design and synthesis of beta-sulfone and alpha-sulfone hydroxamates as potent and orally active MMP inhibitors. 222nd ACS Natl Meet (Aug 26 2001, Chicago) 2001, Abst MEDI 259. |
| 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) | 11176 | 3-Bromopropyne; 3-Bromo-1-propyne | 106-96-7 | C3H3Br | 详情 | 详情 |
| (IX) | 56377 | ethyl 4-[(4-fluorophenyl)sulfonyl]-1-(2-propynyl)-4-piperidinecarboxylate | C17H20FNO4S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IX)Displacement of the 4-fluoro group of (IX) with thiophenol (X) in the presence of K2CO3 led to the diaryl sulfide (XI). Acid (XII), prepared by alkaline hydrolysis of ester (XI), was then coupled to O-tetrahydropyranyl hydroxylamine (XIII) by means of EDC to furnish (XIV). Finally, acidic cleavage of the tetrahydropyranyl moiety produced the corresponding hydroxamic acid.
| 【1】 Becker, D.P.; Hockerman, S.L.; Barta, T.E.; et al.; Design and synthesis of beta-sulfone and alpha-sulfone hydroxamates as potent and orally active MMP inhibitors. 222nd ACS Natl Meet (Aug 26 2001, Chicago) 2001, Abst MEDI 259. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IX) | 56377 | ethyl 4-[(4-fluorophenyl)sulfonyl]-1-(2-propynyl)-4-piperidinecarboxylate | C17H20FNO4S | 详情 | 详情 | |
| (X) | 12951 | Benzenethiol; Phenylmercaptan; Phenylhydrosulfide | 108-98-5 | C6H6S | 详情 | 详情 |
| (XI) | 56378 | ethyl 4-{[4-(phenylsulfanyl)phenyl]sulfonyl}-1-(2-propynyl)-4-piperidinecarboxylate | C23H25NO4S2 | 详情 | 详情 | |
| (XII) | 56379 | 4-{[4-(phenylsulfanyl)phenyl]sulfonyl}-1-(2-propynyl)-4-piperidinecarboxylic acid | C21H21NO4S2 | 详情 | 详情 | |
| (XIII) | 52106 | 2-(aminooxy)tetrahydro-2H-pyran; O-tetrahydro-2H-pyran-2-ylhydroxylamine | C5H11NO2 | 详情 | 详情 | |
| (XIV) | 56380 | 4-{[4-(phenylsulfanyl)phenyl]sulfonyl}-1-(2-propynyl)-N-(tetrahydro-2H-pyran-2-yloxy)-4-piperidinecarboxamide | C26H30N2O5S2 | 详情 | 详情 |