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【结 构 式】 
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【分子编号】36479 【品名】methyl (E)-3-[2-[(1R,2R,3S,6S,7S)-5-oxo-4,10-dioxatricyclo[5.2.1.0(2,6)]dec-3-yl]phenyl]-2-propenoate 【CA登记号】 |
【 分 子 式 】C18H18O5 【 分 子 量 】314.33792 【元素组成】C 68.78% H 5.77% O 25.45% |
合成路线1
该中间体在本合成路线中的序号：(XVIII)The synthesis of [1S-(1alpha,2alpha,3alpha,4alpha)]-2-[2-[2-(methoxycarbonyl)ethyl]benzyl]-7-oxabicyclo[2.2.1]heptane-3-carboxylic acid (VI), a key intermediate in the synthesis of 203961 [see scheme 20396101a] has been presented: This compound has been obtained by two similar ways: 1) The condensation of L-valinol (XII) with anhydride (XXII) catalyzed by oxalic acid gives imide (XIII), which is treated with ethylmagnesium chloride, the Grignard reagent (XIV) and NaBH4 yielding intermediate (XV). This intermediate, without isolation, is treated with HCl in THF to afford the substituted benzaldehyde (XVI), which is condensed with trimethyl phosphonoacetate (XVII) and DBU in acetonitrile giving the propenoic ester (XVIII). Finally, this compound is submitted to a simultaneous reduction and hydrogenolysis with H2 over a Pearlman catalyst in methanol to provide the target of [1S-(1alpha,2alpha,3alpha,4alpha)]-2-[2-[2-(methoxycarbonyl)ethyl]benzyl]-7-oxabicyclo[2.2.1]heptane-3-carboxylic acid (VI). 2) The preceding reaction sequence can also be performed using (S)-2-phenylglycinol (XIX) instead of the L-valinol (XII) yielding the previously reported benzaldehyde (XVI) through the imide (XX) and the nonisolated intermediate (XXI).
| 【1】 Mueller, R.H.; et al.; Diastereoselective reaction of a grignard reagent with chiral imides: A practical preparation of a key intermediate in the synthesis of ifetroban sodium. Org Process Res Dev 1997, 1, 1, 14. |
| 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) | 14870 | (1R,2S,3R,4S)-3-[2-(3-methoxy-3-oxopropyl)benzyl]-7-oxabicyclo[2.2.1]heptane-2-carboxylic acid | C18H22O5 | 详情 | 详情 | |
| (XII) | 36480 | (2S)-2-amino-3-methyl-1-butanol; (S)-(+)-Valinol; L-Valinol | 2026-48-4 | C5H13NO | 详情 | 详情 |
| (XIII) | 36473 | (1R,2R,6S,7S)-4-[(1R)-1-(hydroxymethyl)-2-methylpropyl]-10-oxa-4-azatricyclo[5.2.1.0(2,6)]decane-3,5-dione | C13H19NO4 | 详情 | 详情 | |
| (XIV) | 36475 | bromo[2-(1,3-dioxolan-2-yl)phenyl]magnesium | C9H9BrMgO2 | 详情 | 详情 | |
| (XV) | 36476 | (1S,2S,5R,6R,7R)-4-[(1S)-1,2-dimethylpropyl]-5-[2-(1,3-dioxolan-2-yl)phenyl]-5-hydroxy-10-oxa-4-azatricyclo[5.2.1.0(2,6)]decan-3-one | C22H29NO5 | 详情 | 详情 | |
| (XVI) | 36478 | 2-[(1R,2R,3S,6S,7S)-5-oxo-4,10-dioxatricyclo[5.2.1.0(2,6)]dec-3-yl]benzaldehyde | C15H14O4 | 详情 | 详情 | |
| (XVII) | 13272 | Methyl 2-(dimethoxyphosphoryl)acetate; Trimethyl phosphoroacetate | 5927-18-4 | C5H11O5P | 详情 | 详情 |
| (XVIII) | 36479 | methyl (E)-3-[2-[(1R,2R,3S,6S,7S)-5-oxo-4,10-dioxatricyclo[5.2.1.0(2,6)]dec-3-yl]phenyl]-2-propenoate | C18H18O5 | 详情 | 详情 | |
| (XIX) | 10973 | (2S)-2-Amino-2-phenyl-1-ethanol; (S)-2-Hydroxy-1-phenylethylamine; (S)-(+)-2-Phenylglycinol; (S)-2-Amino-2-phenyl-1-ethanol | 20989-17-7 | C8H11NO | 详情 | 详情 |
| (XX) | 36474 | (1R,2R,6S,7S)-4-[(1R)-2-hydroxy-1-phenylethyl]-10-oxa-4-azatricyclo[5.2.1.0(2,6)]decane-3,5-dione | C16H17NO4 | 详情 | 详情 | |
| (XXI) | 36477 | (1S,2S,5R,6R,7R)-5-[2-(1,3-dioxolan-2-yl)phenyl]-5-hydroxy-4-[(1S)-1-phenylethyl]-10-oxa-4-azatricyclo[5.2.1.0(2,6)]decan-3-one | C25H27NO5 | 详情 | 详情 | |
| (XXII) | 36472 | (1R,2R,6S,7S)-4,10-dioxatricyclo[5.2.1.0(2,6)]decane-3,5-dione | C8H8O4 | 详情 | 详情 |