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【结 构 式】 
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【分子编号】59542 【品名】tert-butyl 4-(4-hydroxybutyl)-1-piperidinecarboxylate 【CA登记号】 |
【 分 子 式 】C14H27NO3 【 分 子 量 】257.37332 【元素组成】C 65.33% H 10.57% N 5.44% O 18.65% |
合成路线1
该中间体在本合成路线中的序号：(VIII)4-Pyridineacetic acid (I) was hydrogenated to the corresponding piperidine (II) in the presence of PtO2. After protection of (II) as the N-Boc derivative (III), reduction of its carboxylate group with borane in THF provided alcohol (IV). Subsequent Swern oxidation of alcohol (IV) furnished aldehyde (V). This was then subjected to a Wittig condensation with carbomethoxytriphenylphosphorane to yield the unsaturated ester (VI), which was further hydrogenated to (VII) in the presence of Pd/C. After saponification of the methyl ester function of (VII), the resultant carboxylic acid was reduced to alcohol (VIII) by means of borane in THF. Conversion of alcohol (VIII) into the alkyl bromide (IX) was accomplished by treatment with carbon tetrabromide and triphenylphosphine. Then, alkylation of the phenolic hydroxyl of N-Cbz-L-tyrosine (X) with bromide (IX) in the presence of NaH in DMF afforded adduct (XI).
| 【1】 Egbertson, M.S.; Laswell, W.L.; Hartman, G.D.; Duggan, M.E.; Halczenko, W. (Merck & Co., Inc.); Novel sulfonamide fibrinogen receptor antagonists. EP 0478363; EP 0743302; JP 1992288051; US 5292756 . |
| 【2】 Egbertson, M.S.; Hartman, G.D.; Halczenko, W.; Laswell, W.L.; Duggan, M.E. (Merck & Co., Inc.); Novel sulfonamide fibrinogen receptor antagonists. WO 9319046 . |
| 【3】 Egbertson, M.S.; Chang, C.T.C.; Duggan, M.E.; et al.; Non-peptide fibrinogen receptor antagonists. 2. Optimization of a tyrosine template as a mimic for Arg-Gly-Asp. J Med Chem 1994, 37, 16, 2537. |
| 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) | 17883 | 2-(4-pyridinyl)acetic acid | 28356-58-3 | C7H7NO2 | 详情 | 详情 |
| (II) | 45854 | 2-(4-piperidinyl)acetic acid; 4-piperidinylacetic acid | 51052-78-9 | C7H13NO2 | 详情 | 详情 |
| (III) | 19346 | 1-Boc-piperidin-4-ylacetic acid; 2-[1-(tert-butoxycarbonyl)-4-piperidinyl]acetic acid | 157688-46-5 | C12H21NO4 | 详情 | 详情 |
| (IV) | 43453 | tert-butyl 4-(2-hydroxyethyl)-1-piperidinecarboxylate | C12H23NO3 | 详情 | 详情 | |
| (V) | 59541 | tert-butyl 4-(2-oxoethyl)-1-piperidinecarboxylate | C12H21NO3 | 详情 | 详情 | |
| (VI) | 45855 | tert-butyl 4-[(E)-4-methoxy-4-oxo-2-butenyl]-1-piperidinecarboxylate | C15H25NO4 | 详情 | 详情 | |
| (VII) | 45856 | tert-butyl 4-(4-methoxy-4-oxobutyl)-1-piperidinecarboxylate | C15H27NO4 | 详情 | 详情 | |
| (VIII) | 59542 | tert-butyl 4-(4-hydroxybutyl)-1-piperidinecarboxylate | C14H27NO3 | 详情 | 详情 | |
| (IX) | 59543 | tert-butyl 4-(4-bromobutyl)-1-piperidinecarboxylate | C14H26BrNO2 | 详情 | 详情 | |
| (X) | 39328 | (2S)-2-[[(benzyloxy)carbonyl]amino]-3-(4-hydroxyphenyl)propionic acid | C17H17NO5 | 详情 | 详情 | |
| (XI) | 59544 | (2S)-2-{[(benzyloxy)carbonyl]amino}-3-(4-{4-[1-(tert-butoxycarbonyl)-4-piperidinyl]butoxy}phenyl)propanoic acid | C31H42N2O7 | 详情 | 详情 |