【结 构 式】 |
【分子编号】39345 【品名】2-(5-chloro-2-methoxyphenyl)-2-fluoro-2-[2-nitro-4-(trifluoromethyl)phenyl]acetic acid 【CA登记号】 |
【 分 子 式 】C16H10ClF4NO5 【 分 子 量 】407.7054528 【元素组成】C 47.14% H 2.47% Cl 8.7% F 18.64% N 3.44% O 19.62% |
合成路线1
该中间体在本合成路线中的序号:(XIII)A chiral process for the synthesis of the title compound was later reported. Chlorination of 2-methoxyphenylacetic acid (VII) with sulfuryl chloride gave (VIII), which was further converted to the corresponding methyl ester (IX) by treatment with dimethyl sulfate and K2CO3. Conversion of (IX) to the lithium enolate with lithium hexamethyldisilazide, followed by condensation with aryl fluoride (X) yielded the diarylacetic ester (XI). This was reacted with N-fluoro-bis(phenylsulfonyl)amine to provide fluoro ester (XII). Basic hydrolysis afforded the racemic carboxylic acid (XIII), which was resolved via conversion to the diastereoisomeric salts with (S)-alpha-methylbenzylamine. Reduction of the nitro group from the desired (S)-enantiomer (XIV), and subsequent acidic treatment then produced the title oxindole derivative.
【1】 Hewawasam, P.; et al.; The synthesis and characterization of BMS-204352 (MaxiPost) and related 3-fluorooxindoles as openers of maxi-K potassium channels. Bioorg Med Chem Lett 2002, 12, 7, 1023. |
【2】 Martín, L.; Castañer, R.M.; Sorbera, L.A.; Castañer, J.; BMS-204352. Drugs Fut 2001, 26, 1, 9. |
【3】 Thottathil, J.K.; Pendri, Y.R.; Martinez, E.J.; Hewawasam, P. (Bristol-Myers Squibb Co.); Preparation of 3-fluoro oxindole derivs.. WO 9816222 . |
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) | 19706 | 2-(2-methoxyphenyl)acetic acid | 93-25-4 | C9H10O3 | 详情 | 详情 |
(VIII) | 39340 | 2-(5-chloro-2-methoxyphenyl)acetic acid | C9H9ClO3 | 详情 | 详情 | |
(IX) | 39341 | methyl 2-(5-chloro-2-methoxyphenyl)acetate | C10H11ClO3 | 详情 | 详情 | |
(X) | 39342 | 1-fluoro-2-nitro-4-(trifluoromethyl)benzene | 367-86-2 | C7H3F4NO2 | 详情 | 详情 |
(XI) | 39343 | methyl 2-(5-chloro-2-methoxyphenyl)-2-[2-nitro-4-(trifluoromethyl)phenyl]acetate | C17H13ClF3NO5 | 详情 | 详情 | |
(XII) | 39344 | methyl 2-(5-chloro-2-methoxyphenyl)-2-fluoro-2-[2-nitro-4-(trifluoromethyl)phenyl]acetate | C17H12ClF4NO5 | 详情 | 详情 | |
(XIII) | 39345 | 2-(5-chloro-2-methoxyphenyl)-2-fluoro-2-[2-nitro-4-(trifluoromethyl)phenyl]acetic acid | C16H10ClF4NO5 | 详情 | 详情 | |
(XIV) | 39346 | (2S)-2-(5-chloro-2-methoxyphenyl)-2-fluoro-2-[2-nitro-4-(trifluoromethyl)phenyl]ethanoic acid | C16H10ClF4NO5 | 详情 | 详情 |