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【结 构 式】 
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【分子编号】19748 【品名】(1S,5R)-2-[(1S)-1-phenylethyl]-6-oxa-2-azabicyclo[3.2.1]octan-7-one 【CA登记号】 |
【 分 子 式 】C14H17NO2 【 分 子 量 】231.29452 【元素组成】C 72.7% H 7.41% N 6.06% O 13.83% |
合成路线1
该中间体在本合成路线中的序号：(XXVII)The chiral piperidine (2S,4R)(VI) has been obtained as follows: The cyclization of 3-buten-1-ol (XXII) with (S)-1-phenylethylamine (XXIII) and glyoxylic acid (XXIV) by means of tosyl chloride in THF gives a mixture of the (2S,4R) and (2R,4S) lactones (XXV), which is resolved by fractional crystallyzation of their salts with the chiral camphorsulfonic acid (XXVI), followed by elimination of the acid with ammonia to afford (2S,4R)(XXVII). The reaction of lactone (XXVII) with isopropylmagnesium chloride and tert-butylamine in THF gives (2S,4R)-N-tert-butyl-4-hydroxy-1-(1(S)-phenylethyl)piperidine-2-carboxamide (XXVIII), which is debenzylated by hydrogenation and protected with tert-butoxycarbonyl anhydride yielding (2S,4R)-N-(tert-butoxycarbonyl)-4-hydroxypiperidine-2-carboxamide (2S,4R)(XI), which is finally condensed with 4-(chloromethyl)pyridine (XII) as before to obtain the chiral piperidine (2S,4R)(VI), already reported.
| 【1】 Beaulieu, P.L.; et al.; Practical, stereoselective synthesis of palinavir, a potent HIV protease inhibitor. J Org Chem 1997, 62, 11, 3440. |
| 【2】 Gillard, J.; et al.; Preparation of (2S,4R)-4-hydroxypipecolic acid and derivatives. J Org Chem 1996, 61, 6, 2226. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VI) | 19731 | (2S,4R)-N-(tert-butyl)-4-(4-pyridinylmethoxy)-2-piperidinecarboxamide | C16H25N3O2 | 详情 | 详情 | |
| (XI) | 19736 | tert-butyl (2S,4R)-2-[(tert-butylamino)carbonyl]-4-hydroxy-1-piperidinecarboxylate | C15H28N2O4 | 详情 | 详情 | |
| (XII) | 10844 | 4-(Chloromethyl)pyridine | 10445-91-7 | C6H6ClN | 详情 | 详情 |
| (XXII) | 19743 | 3-buten-1-ol | 627-27-0 | C4H8O | 详情 | 详情 |
| (XXIII) | 10039 | (1R)-1-Phenylethylamine; (1R)-1-Phenyl-1-ethanamine.; L-alpha-Phenylethylamine | 3886-69-9 | C8H11N | 详情 | 详情 |
| (XXIV) | 15618 | 2-Oxoacetic acid; Glyoxylic Acid | 298-12-4 | C2H2O3 | 详情 | 详情 |
| (XXV) | 19746 | 2-[(1S)-1-phenylethyl]-6-oxa-2-azabicyclo[3.2.1]octan-7-one | C14H17NO2 | 详情 | 详情 | |
| (XXVI) | 19747 | (3-bromo-1,7-dimethyl-2-oxobicyclo[2.2.1]hept-7-yl)methanesulfonic acid | C10H15BrO4S | 详情 | 详情 | |
| (XXVII) | 19748 | (1S,5R)-2-[(1S)-1-phenylethyl]-6-oxa-2-azabicyclo[3.2.1]octan-7-one | C14H17NO2 | 详情 | 详情 | |
| (XXVIII) | 19749 | (2S,4R)-N-(tert-butyl)-4-hydroxy-1-[(1S)-1-phenylethyl]-2-piperidinecarboxamide | C18H28N2O2 | 详情 | 详情 |