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【结 构 式】 
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【分子编号】62027 【品名】(1R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl 4,4,4-trifluoro-3-oxobutanoate 【CA登记号】 |
【 分 子 式 】C14H19F3O3 【 分 子 量 】292.2982696 【元素组成】C 57.53% H 6.55% F 19.5% O 16.42% |
合成路线1
该中间体在本合成路线中的序号：(III)The reaction of trifluoroacetoacetic acid ethyl ester (I) with (?)-isoborneol (II) at 130 C gives the corresponding isobornyl ester (III), which is condensed with cyclohexane-1,3-dione (IV) and 3-cyanobenzaldehyde (V) by means of ammonium acetate in refluxing ethanol to yield the octahydroquinolone (VI). The hydrolysis of the ester group of (VI), with simultaneous dehydration by means of TsOH in refluxing toluene affords 4-(3-cyanophenyl)-5-oxo-2-(trifluoromethyl)-1,4,5,6,7,8-hexahydroquinoline-3-carboxylic acid (VII) as a racemic mixture. Optical resolution of (VII) through the diastereomeric salt with 1(S)-phenylethylamine (VIII) in toluene/butanol provides the desired isomer (IX), which is finally decarboxylated in N-methyl-2-pyrrolidone at 210 C to furnish the target hexahydroquinolone.
| 【1】 Ashworth, I.; Hopes, P.; Levin, D.; Patel, I.; Salloo, R.; An asymmetric synthesis of a 4-substituted-1,4-dihydropyridine. Tetrahedron Lett 2002, 43, 28, 4931. |
| 【2】 Warawa, J.E.; Ohnmacht, C.J. Jr.; Trainor, D.A.; Hulsizer, J.M. (AstraZeneca plc); Quinolone deriv. for treatment of urinary incontinence. EP 0755382; JP 1997512254; WO 9528388 . |
| 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) | 62025 | propyl 4,4,4-trifluoro-3-oxobutanoate | C7H9F3O3 | 详情 | 详情 | |
| (II) | 62026 | (1R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol | C10H18O | 详情 | 详情 | |
| (III) | 62027 | (1R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl 4,4,4-trifluoro-3-oxobutanoate | C14H19F3O3 | 详情 | 详情 | |
| (IV) | 11244 | 1,3-Cyclohexanedione | 504-02-9 | C6H8O2 | 详情 | 详情 |
| (V) | 13245 | 3-Formylbenzonitrile; 3-Cyanobenzaldehyde | 24964-64-5 | C8H5NO | 详情 | 详情 |
| (VI) | 62028 | (1R)-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl 4-(3-cyanophenyl)-2-hydroxy-5-oxo-2-(trifluoromethyl)-1,2,3,4,5,6,7,8-octahydro-3-quinolinecarboxylate | C28H31F3N2O4 | 详情 | 详情 | |
| (VII) | 62029 | 4-(3-cyanophenyl)-5-oxo-2-(trifluoromethyl)-1,4,5,6,7,8-hexahydro-3-quinolinecarboxylic acid | C18H13F3N2O3 | 详情 | 详情 | |
| (VIII) | 10039 | (1R)-1-Phenylethylamine; (1R)-1-Phenyl-1-ethanamine.; L-alpha-Phenylethylamine | 3886-69-9 | C8H11N | 详情 | 详情 |
| (IX) | 62030 | (4S)-4-(3-cyanophenyl)-5-oxo-2-(trifluoromethyl)-1,4,5,6,7,8-hexahydro-3-quinolinecarboxylic acid | C18H13F3N2O3 | 详情 | 详情 |