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【结 构 式】 
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【分子编号】35255 【品名】1-[2-(2-thienyl)ethyl]-4-piperidinone 【CA登记号】 |
【 分 子 式 】C11H15NOS 【 分 子 量 】209.31224 【元素组成】C 63.12% H 7.22% N 6.69% O 7.64% S 15.32% |
合成路线1
该中间体在本合成路线中的序号：(IV)A total synthesis of sufentanil has been described: The cyclization of 2-(2-thienyl)ethylamine (I) with allyltrimethylsilane (II) and formaldehyde gives 4-hydroxy-1-[2-(2-thienyl)ethyl]piperidine (III), which is oxidized with oxalyl chloride in DMSO/dichloromethane to 1-[2-(2-thienyl)ethyl]piperidin-4-one (IV). The epoxidation of (IV) by means of trimethylsulfonium iodide and the sodium salt of DMSO yields the spiro-epoxide (V), which is opened with aniline (VI) and boron trifluoride ethearate giving a 1.8:1 mixture of 4-(hydroxymethyl)-4-(phenylamino)piperidine (VII) and 4-hydroxy-4-(phenylamino)piperidine (VIII) that are conveniently separated. The methylation of the OH group of (VII) with diazomethane and SiO2 affords the methoxymethyl compound (IX), which is finally acylated with propionic anhydride to provide sufentanil.
| 【1】 Park, H.J.; Jeon, R.O.; Ryu, J.S.; Hyun, S.S.; Suh, Y.G.; Shin, D.Y.; Total synthesis of sufentanil. Arch Pharmacal Res 1999, 22, 4, 398. |
| 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) | 35253 | 2-(2-thienyl)ethylamine; 2-(2-thienyl)-1-ethanamine; 2-Thiophene ethylamine | 30433-91-1 | C6H9NS | 详情 | 详情 |
| (II) | 15775 | Allyltrimethylsilane; allyl(trimethyl)silane | 762-72-1 | C6H14Si | 详情 | 详情 |
| (III) | 35254 | 1-[2-(2-thienyl)ethyl]-4-piperidinol | C11H17NOS | 详情 | 详情 | |
| (IV) | 35255 | 1-[2-(2-thienyl)ethyl]-4-piperidinone | C11H15NOS | 详情 | 详情 | |
| (V) | 35256 | 6-[2-(2-thienyl)ethyl]-1-oxa-6-azaspiro[2.5]octane | C12H17NOS | 详情 | 详情 | |
| (VI) | 12294 | Aniline; Phenylamine | 62-53-3 | C6H7N | 详情 | 详情 |
| (VII) | 35257 | [4-anilino-1-[2-(2-thienyl)ethyl]-4-piperidinyl]methanol | C18H24N2OS | 详情 | 详情 | |
| (VIII) | 35258 | 4-(anilinomethyl)-1-[2-(2-thienyl)ethyl]-4-piperidinol | C18H24N2OS | 详情 | 详情 | |
| (IX) | 35259 | N-[4-(methoxymethyl)-1-[2-(2-thienyl)ethyl]-4-piperidinyl]-N-phenylamine; 4-(methoxymethyl)-N-phenyl-1-[2-(2-thienyl)ethyl]-4-piperidinamine | C19H26N2OS | 详情 | 详情 |