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【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%

与该中间体有关的原料药合成路线共 1 条

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
Extended Information