【结 构 式】 |
【分子编号】14783 【品名】(4R,5S)-4-Methyl-5-phenyl-3-(4,4,4-trifluorobutanoyl)-1,3-oxazolan-2-one 【CA登记号】 |
【 分 子 式 】C14H14F3NO3 【 分 子 量 】301.2653096 【元素组成】C 55.82% H 4.68% F 18.92% N 4.65% O 15.93% |
合成路线1
该中间体在本合成路线中的序号:(XIII)The synthesis of the key chiral amine component (VII) is outlined: Conversion of 4,4,4-trifluorobutyric acid (XI) to the corresponding acid chloride and subsequent reaction with the anion derived from the Evans oxazolidinone (XII) yielded the acyloxazolidinone (XIII). Treatment of (XIII) with a strong base such as sodium hexamethyldisilazide and alkylation of the resultant enolate with iodomethane at -35 C afforded a mixture of the diastereomeric acyloxazolidinones (XIV). The desired diastereomer was obtained by crystallization of the crude product. Reductive cleavage of the chiral auxiliary gave the enantiomerically pure alcohol (XV), which was converted in two steps to the desired enantiomerically pure amine hydrochloride (VII). Alternative routes to the amine, such as resolution of racemic 4,4,4-trifluoro-2-methylbutyric acid followed by amide formation and reduction to (VII) could also be utilized.
【1】 Bernstein, P.R.; Jacobs, R.T.; ZD 3523. Drugs Fut 1995, 20, 12, 1233. |
【2】 Jacobs, R.T.; Yee, Y.K.; Bernstein, P.R.; Brewster, A.G.; Sependa, G.J. (AstraZeneca plc); A process for the preparation of 2(R)-methyl-4,4,4-trifluorobutylamine, intermediates and a process for the preparation of a derivative thereof. EP 0489548 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
12376 | Phthalimide; 1H-Isoindole-1,3(2H)-dione; Isoindole-1,3-dione;Phthalic dicarboximide;Phenylimide;Isoindole-1,3-dione | 85-41-6 | C8H5NO2 | 详情 | 详情 | |
(XI) | 14781 | 4,4,4-Trifluorobutyric acid | 406-93-9 | C4H5F3O2 | 详情 | 详情 |
(XII) | 14782 | [(4R,5S)-4-Methyl-2-oxo-5-phenyl-1,3-oxazolidin-3-yl]lithium | C10H10LiNO2 | 详情 | 详情 | |
(XIII) | 14783 | (4R,5S)-4-Methyl-5-phenyl-3-(4,4,4-trifluorobutanoyl)-1,3-oxazolan-2-one | C14H14F3NO3 | 详情 | 详情 | |
(XIV) | 14784 | (4R,5S)-4-methyl-5-phenyl-3-[(2R)-4,4,4-trifluoro-2-methylbutyl]-1,3-oxazolan-2-one | C15H18F3NO2 | 详情 | 详情 | |
(XV) | 14785 | (2R)-4,4,4-trifluoro-2-methyl-1-butanol | 107103-95-7 | C5H9F3O | 详情 | 详情 |
(XVI) | 14786 | 2-[(2R)-4,4,4-trifluoro-2-methylbutyl]-1H-isoindole-1,3(2H)-dione | C13H12F3NO2 | 详情 | 详情 |