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【结 构 式】 
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【分子编号】32338 【品名】1-[2-chloro-4-(chloromethyl)-5-oxo-2,5-dihydro-3-furanyl]propyl benzoate 【CA登记号】 |
【 分 子 式 】C15H14Cl2O4 【 分 子 量 】329.17916 【元素组成】C 54.73% H 4.29% Cl 21.54% O 19.44% |
合成路线1
该中间体在本合成路线中的序号：(VIII)The cyclization of N-(ethoxycarbonyl)glycine ethyl ester (I) with ethyl acrylate (II) by means of NaH in refluxing benzene gives 4-oxopyrrolidine-1,3-dicarboxylic acid diethyl ester (III), which is selectively decarboxylated with refluxing aqueous 6N HCl yielding 3-oxopyrrolidine-1-carboxylic acid ethyl ester (IV). The Friedlander cyclization of (IV) with 2-aminobenzaldehyde (V) affords the pyrroloquinoline derivative (VI), which is decarboxylated in basic medium to afford 2,3-dihydro-1H-pyrrolo[3,4-b]quinoline (VII). The condensation of (VII) with the furanone derivative (VIII) by means of pyridine in acetonitrile affords the acylated pyrroloquinoline (IX), which is cyclized by means of NaOAc in acetic acid providing the tetracyclic intermediate (X). The dechlorination of (X) with H2 over Pd/C in ethanol affords the expected methyl derivative (XI), which is debenzoylated with sodium methoxide in methanol to give the secondary alcohol (XII). Finally, this compound is oxidized with pyridinium chlorochromate (PCC) in dichloromethane.
| 【1】 Yadav, J.S.; et al.; A convergent total synthesis of mappicine ketone: A leading antiviral compound. Tetrahedron 1999, 55, 17, 5449. |
| 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) | 32333 | ethyl 2-[(ethoxycarbonyl)amino]acetate | C7H13NO4 | 详情 | 详情 | |
| (II) | 10164 | ethyl acrylate | 140-88-5 | C5H8O2 | 详情 | 详情 |
| (III) | 32334 | diethyl 4-oxo-1,3-pyrrolidinedicarboxylate | C10H15NO5 | 详情 | 详情 | |
| (IV) | 32335 | ethyl 3-oxo-1-pyrrolidinecarboxylate | C7H11NO3 | 详情 | 详情 | |
| (V) | 18302 | 2-Aminobenzaldehyde | 529-23-7 | C7H7NO | 详情 | 详情 |
| (VI) | 32336 | ethyl 1,3-dihydro-2H-pyrrolo[3,4-b]quinoline-2-carboxylate | C14H14N2O2 | 详情 | 详情 | |
| (VII) | 32337 | 2,3-dihydro-1H-pyrrolo[3,4-b]quinoline | C11H10N2 | 详情 | 详情 | |
| (VIII) | 32338 | 1-[2-chloro-4-(chloromethyl)-5-oxo-2,5-dihydro-3-furanyl]propyl benzoate | C15H14Cl2O4 | 详情 | 详情 | |
| (IX) | 32339 | (E)-3-(chloromethyl)-4-(1,3-dihydro-2H-pyrrolo[3,4-b]quinolin-2-yl)-1-ethyl-2-formyl-4-oxo-2-butenyl benzoate | C26H23ClN2O4 | 详情 | 详情 | |
| (X) | 32340 | 1-[8-(chloromethyl)-9-oxo-9,11-dihydroindolizino[1,2-b]quinolin-7-yl]propyl benzoate | C26H21ClN2O3 | 详情 | 详情 | |
| (XI) | 32341 | 1-(8-methyl-9-oxo-9,11-dihydroindolizino[1,2-b]quinolin-7-yl)propyl benzoate | C26H22N2O3 | 详情 | 详情 | |
| (XII) | 32342 | 7-(1-hydroxypropyl)-8-methylindolizino[1,2-b]quinolin-9(11H)-one | C19H18N2O2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VIII)The intermediate, the furanone derivative (VIII) has been obtained as follows: The reaction of propargyl alcohol (XIII) with dihydropyran and Ts-OH gives the tetrahydropyranyl ether (XIV), which is treated with ethylmagnesium bromide to yield the corresponding magnesium derivative (XV). The reaction of (XV) with propionaldehyde (XVI) in THF affords the secondary alcohol (XVII), which is benzoylated with benzoyl chloride and triethylamine affording the benzoate (XVIII). The deprotection of (XVIII) with Ts-OH gives the primary alcohol (XIX), which is oxidized with pyridinium chlorochromate (PCC) to the corresponding aldehyde (XX). The Diels-Alder reaction of (XX) with 5-ethoxy-4-methyloxazole (XXI) in refluxing toluene yields 4-(1-benzoyloxypropyl)-2-ethoxyfuran-3-carbaldehyde (XXII), which is reduced with NaBH4 in methanol to the carbinol (XXIII). The controlled oxidation of (XXIII) with MnO2/HCl affords 4-(1-benzoyloxypropyl)-5-hydroxy-3-(hydroxymethyl)furan-2(5H)-one (XXIV), which is finally treated with SOCl2 and DMF in chloroform to afford the target intermediate (VIII).
| 【1】 Yadav, J.S.; et al.; A convergent total synthesis of mappicine ketone: A leading antiviral compound. Tetrahedron 1999, 55, 17, 5449. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VIII) | 32338 | 1-[2-chloro-4-(chloromethyl)-5-oxo-2,5-dihydro-3-furanyl]propyl benzoate | C15H14Cl2O4 | 详情 | 详情 | |
| (XIII) | 16664 | Propargyl Alcohol; 2-propyn-1-ol | 107-19-7 | C3H4O | 详情 | 详情 |
| (XIV) | 32343 | 2-(3-butynyloxy)tetrahydro-2H-pyran; 3-butynyl tetrahydro-2H-pyran-2-yl ether | 40365-61-5 | C9H14O2 | 详情 | 详情 |
| (XV) | 32344 | bromo[4-(tetrahydro-2H-pyran-2-yloxy)-1-butynyl]magnesium | C9H13BrMgO2 | 详情 | 详情 | |
| (XVI) | 15966 | propionaldehyde | 123-38-6 | C3H6O | 详情 | 详情 |
| (XVII) | 32345 | 7-(tetrahydro-2H-pyran-2-yloxy)-4-heptyn-3-ol | C12H20O3 | 详情 | 详情 | |
| (XVIII) | 32346 | 1-ethyl-5-(tetrahydro-2H-pyran-2-yloxy)-2-pentynyl benzoate | C19H24O4 | 详情 | 详情 | |
| (XIX) | 32347 | 1-ethyl-4-hydroxy-2-butynyl benzoate | C13H14O3 | 详情 | 详情 | |
| (XX) | 32348 | 1-ethyl-4-oxo-2-butynyl benzoate | C13H12O3 | 详情 | 详情 | |
| (XXI) | 32349 | 5-ethoxy-4-methyl-1,3-oxazole; ethyl 4-methyl-1,3-oxazol-5-yl ether | C6H9NO2 | 详情 | 详情 | |
| (XXII) | 32350 | 1-(5-ethoxy-4-formyl-3-furyl)propyl benzoate | C17H18O5 | 详情 | 详情 | |
| (XXIII) | 32351 | 1-[5-ethoxy-4-(hydroxymethyl)-3-furyl]propyl benzoate | C17H20O5 | 详情 | 详情 | |
| (XXIV) | 32352 | 1-[2-hydroxy-4-(hydroxymethyl)-5-oxo-2,5-dihydro-3-furanyl]propyl benzoate | C15H16O6 | 详情 | 详情 |