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【结 构 式】 
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【分子编号】57373 【品名】4-ethyl 1-methyl 3-oxo-1,4-piperidinedicarboxylate 【CA登记号】 |
【 分 子 式 】C10H15NO5 【 分 子 量 】229.23284 【元素组成】C 52.4% H 6.6% N 6.11% O 34.9% |
合成路线1
该中间体在本合成路线中的序号：(IV)The deprotection of 1-benzyl-2-oxopiperidine-3-carboxylic acid ethyl ester (I) by hydrogenation with H2 over Pd/C in aq. ethanol gives 2-oxopiperidine-3-carboxylic acid ethyl ester (II), which is condensed with methyl chloroformate (III) and K2CO3 in water to yield 1-(methoxycarbonyl)-2-oxopiperidine-3-carboxylic acid ethyl ester (IV). The reaction of (IV) with ethyleneglycol (V) and Ts-OH in refluxing benzene affords the ethylene ketal (VI), which is treated with hydroxylamine and KOH in methanol to provide the carbohydroxamic acid (VII). The cyclization of (VII) by means of hot conc. HCl or HClO4 gives 3-hydroxy-4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridine-6-carboxylic acid methyl ester (VIII), which is finally treated with HBr in refluxing acetic acid and neutralized with TEA to yield the target isoxazolo-pyridine derivative.
| 【1】 Krogsgaard-Larsen, P. (H. Lundbeck A/S); Heterocyclic cpds.. EP 0000167; EP 0000338; EP 0027279; EP 0028017; US 4278676; US 4301287 . |
| 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) | 57371 | ethyl 1-benzyl-3-oxo-4-piperidinecarboxylate | C15H19NO3 | 详情 | 详情 | |
| (II) | 57372 | ethyl 3-oxo-4-piperidinecarboxylate | C8H13NO3 | 详情 | 详情 | |
| (III) | 16993 | methyl chlorocarbonate;Carbonochloridic acid methyl ester；[(chlorocarbonyl)oxy]methane；methyl chloroformate | 79-22-1 | C2H3ClO2 | 详情 | 详情 |
| (IV) | 57373 | 4-ethyl 1-methyl 3-oxo-1,4-piperidinedicarboxylate | C10H15NO5 | 详情 | 详情 | |
| (V) | 11295 | Polyethylene glycol;1,2-Ethanediol;Monoethylene glycol; Ethylene glycol | 107-21-1 | C2H6O2 | 详情 | 详情 |
| (VI) | 43675 | 10-ethyl 7-methyl 1,4-dioxa-7-azaspiro[4.5]decane-7,10-dicarboxylate | C12H19NO6 | 详情 | 详情 | |
| (VII) | 43676 | methyl 10-[(hydroxyamino)carbonyl]-1,4-dioxa-7-azaspiro[4.5]decane-7-carboxylate | C10H16N2O6 | 详情 | 详情 | |
| (VIII) | 43677 | methyl 3-hydroxy-4,7-dihydroisoxazolo[5,4-c]pyridine-6(5H)-carboxylate | C8H10N2O4 | 详情 | 详情 |