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【结 构 式】 
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【分子编号】43669 【品名】4-ethyl 1-methyl (3S,4S)-3-hydroxy-1,4-piperidinedicarboxylate 【CA登记号】 |
【 分 子 式 】C10H17NO5 【 分 子 量 】231.24872 【元素组成】C 51.94% H 7.41% N 6.06% O 34.59% |
合成路线1
该中间体在本合成路线中的序号：(VIII)The alcoholysis of 1-benzyl-2-pyrrolidinone (I) with HCl in ethanol gives 4-(benzylamino)butyric acid ethyl ester (II), which is condensed with ethyl 2-bromoacetate (III) to yield the tertiary amine (IV). The cyclization of (IV) by means of NaOEt affords 1-benzyl-3-hydroxy-1,2,5,6-tetrahydropyridine-4-carboxylic acid ethyl ester (V), which by hydrogenolytic debenzylation, followed by reaction with methyl chloroformate (VI), affords the 1,4-dicarboxylate (VII). The reduction of (VII) with H2 over Ni gives the cis-3-hydroxy-1,4-dicarboxylate (VIII), which is hydrolyzed and selectively decarboxylated with HCl, yielding cis-3-hydroxypiperidine-4-carboxylic acid (IX). Finally, this compound is dehydrated by means of HBr and TEA.
| 【1】 Christensen, V.; Krogsgaard-Larsen, P.; Falch, E.; Chemistry and pharmacology of the GABA agonists THIP (Gabodaxol) and isoguvacine. Drugs Fut 1984, 9, 8, 597. |
| 【2】 Johnston, G.A.R.; Krogsgaard-Larsen, P.; Structure-activity studies on the inhibition of GABA binding to rat brain membranes by muscinol and related compounds. J Neurochem 1978, 30, 1377-1382. |
| 【3】 Krogsgaard-Larsen, P.; Christensen, T.R.; GABA agonists. Synthesis and structure-activity studies on analogues of isoguvacine and THIP. Eur J Med Chem 1979, 14, 157-164. |
| 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) | 43664 | 1-benzyl-2-pyrrolidinone | 5291-77-0 | C11H13NO | 详情 | 详情 |
| (II) | 43665 | ethyl 4-(benzylamino)butanoate | C13H19NO2 | 详情 | 详情 | |
| (III) | 16640 | Ethyl 2-bromoacetate; Ethyl bromoacetate | 105-36-2 | C4H7BrO2 | 详情 | 详情 |
| (IV) | 43666 | ethyl 4-[benzyl(2-ethoxy-2-oxoethyl)amino]butanoate | C17H25NO4 | 详情 | 详情 | |
| (V) | 43667 | ethyl 1-benzyl-5-hydroxy-1,2,3,6-tetrahydro-4-pyridinecarboxylate | C15H19NO3 | 详情 | 详情 | |
| (VI) | 16993 | methyl chlorocarbonate;Carbonochloridic acid methyl ester；[(chlorocarbonyl)oxy]methane；methyl chloroformate | 79-22-1 | C2H3ClO2 | 详情 | 详情 |
| (VII) | 43668 | 4-ethyl 1-methyl 5-hydroxy-3,6-dihydro-1,4(2H)-pyridinedicarboxylate | C10H15NO5 | 详情 | 详情 | |
| (VIII) | 43669 | 4-ethyl 1-methyl (3S,4S)-3-hydroxy-1,4-piperidinedicarboxylate | C10H17NO5 | 详情 | 详情 | |
| (IX) | 43670 | (3S,4S)-3-hydroxy-4-piperidinecarboxylic acid | C6H11NO3 | 详情 | 详情 |