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【结 构 式】 
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【分子编号】30111 【品名】tert-butyl 2-(3-hydroxy-1-azabicyclo[2.2.2]oct-3-yl)acetate 【CA登记号】 |
【 分 子 式 】C13H23NO3 【 分 子 量 】241.33056 【元素组成】C 64.7% H 9.61% N 5.8% O 19.89% |
与该中间体有关的原料药合成路线共 1 条
合成路线1
该中间体在本合成路线中的序号：(II)Condensation of 3-quinuclidinone (I) with tert-butyl acetate using LDA in THF at low temperature gave hydroxy ester (II). Acid cleavage of the tert-butyl ester of (II), followed by esterification with MeOH and H2SO4 produced the methyl ester (III), which was transformed to hydrazide (IV) upon treatment with hydrazine in refluxing MeOH. Nitrosation of (IV) with NaNO2 and HCl, followed by Curtius rearrangement of the intermediate acyl azide furnished the target spiro oxazolidinone (V). The required (S)-enantiomer was then isolated by resolution with dibenzoyl-D-tartaric acid.
| 【1】 Mullen, G.; Balestra, M.; Napier, J.; et al.; (-)-Spiro[1-azabicyclo[2.2.2]octane-3,5'-oxazolidin-2'-one], a conformationally restricted analogue of acetylcholine, is a highly selective full agonist at the alpha7 nicotinic acetylcholine receptor. J Med Chem 2000, 43, 22, 4045. |
| 【2】 Napier, J.; Mack, R.; Loch, J. III; et al.; The synthesis and nicotinic receptor subtype profile of AR-R17779, a conformationally restricted analog of acetylcholine. 15th European Federation for Medicinal Chemistry International Symposium on Medicinal Chemistry (Sept 6 1998, Edinburgh) 1998, Abst P.149. |
| 【3】 Murray, R.J.; Gordon, J.C.; Griffith, R.C.; Balestra, M. (AstraZeneca plc); Spiro-azabicyclic cpds. useful in therapy. WO 9606098 . |
| 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) | 16925 | 3-quinuclidinone; 1-azabicyclo[2.2.2]octan-3-one | 1193-65-3 | C7H11NO | 详情 | 详情 |
| (II) | 30111 | tert-butyl 2-(3-hydroxy-1-azabicyclo[2.2.2]oct-3-yl)acetate | C13H23NO3 | 详情 | 详情 | |
| (III) | 30112 | methyl 2-(3-hydroxy-1-azabicyclo[2.2.2]oct-3-yl)acetate | C10H17NO3 | 详情 | 详情 | |
| (IV) | 30113 | 2-(3-hydroxy-1-azabicyclo[2.2.2]oct-3-yl)acetohydrazide | C9H17N3O2 | 详情 | 详情 | |
| (V) | 30114 | Spiro[oxazolidine-5,3'-quinuclidin]-2-one | C9H14N2O2 | 详情 | 详情 |
Extended Information