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【结 构 式】 
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【分子编号】62468 【品名】(4S)-4-isopropyl-3-[(Z)-2-(methoxymethoxy)-3-(4-methoxyphenyl)-2-propenoyl]-1,3-oxazolidin-2-one 【CA登记号】 |
【 分 子 式 】C18H23NO6 【 分 子 量 】349.38376 【元素组成】C 61.88% H 6.64% N 4.01% O 27.48% |
合成路线1
该中间体在本合成路线中的序号：(LII)Aldol condensation of anisaldehyde (X) with the lithium enolate of the N-acyl oxazolidinone (XLIX) gave adduct (L). Dehydration of alcohol (L) was accomplished by formation of the corresponding mesylate (LI), which underwent elimination in the presence of DBU, to produce a 4:1 mixture of Z and E olefins. After chromatographic isolation of the major Z isomer (LII), diastereoselective Michael addition using a 1:2 mixture of 2-aminothiophenol (VII) and the corresponding lithium thiophenoxide furnished (LIII) as the major diastereoisomer. Intramolecular cyclization of the amino imide (LIII) to the benzothiazepinone (LIV) was accomplished in the presence of trimethylaluminium in refluxing CH2Cl2. The methoxymethyl group of (LIV) was then removed by treatment with TiCl4, leading to the key precursor the thiazepinone (VIII)
| 【1】 Miyata, O.; Shinada, T.; Ninomiya, I.; Naito, T.; Asymmetric construction of two contiguous stereocenters by diastereoface differentiating addition reaction of thiols to chiral imides: Formal synthesis of (+)-diltiazem. Tetrahedron 1997, 53, 7, 2421. |
| 【2】 Miyata, O.; Shinada, T.; Ninomiya, I.; Naito, T.; Asymmetric induction at two contiguous stereogenic centers by diastereoface differentiating nucleophilic addition reaction. Tetrahedron Lett 1991, 32, 29, 3519. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VII) | 25182 | 2-aminobenzenethiol | 137-07-5 | C6H7NS | 详情 | 详情 |
| (VIII) | 62436 | (2S,3S)-3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one | C16H15NO3S | 详情 | 详情 | |
| (X) | 27251 | 4-methoxybenzaldehyde; Anisicaldehyde; p-anisaldehyde | 123-11-5 | C8H8O2 | 详情 | 详情 |
| (XLIX) | 62465 | (4S)-4-isopropyl-3-[2-(methoxymethoxy)acetyl]-1,3-oxazolidin-2-one | C10H17NO5 | 详情 | 详情 | |
| (L) | 62466 | (4S)-3-[3-hydroxy-2-(methoxymethoxy)-3-(4-methoxyphenyl)propanoyl]-4-isopropyl-1,3-oxazolidin-2-one | C18H25NO7 | 详情 | 详情 | |
| (LI) | 62467 | 3-[(4S)-4-isopropyl-2-oxo-1,3-oxazolidin-3-yl]-2-(methoxymethoxy)-1-(4-methoxyphenyl)-3-oxopropyl methanesulfonate | C19H27NO9S | 详情 | 详情 | |
| (LII) | 62468 | (4S)-4-isopropyl-3-[(Z)-2-(methoxymethoxy)-3-(4-methoxyphenyl)-2-propenoyl]-1,3-oxazolidin-2-one | C18H23NO6 | 详情 | 详情 | |
| (LIII) | 62469 | (4S)-3-[(2S,3S)-3-[(2-aminophenyl)sulfanyl]-2-(methoxymethoxy)-3-(4-methoxyphenyl)propanoyl]-4-isopropyl-1,3-oxazolidin-2-one | C24H30N2O6S | 详情 | 详情 | |
| (LIV) | 62470 | (2S,3S)-3-(methoxymethoxy)-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4(5H)-one | C18H19NO4S | 详情 | 详情 |