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【结 构 式】 
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【分子编号】17125 【品名】(2S)-2-[(2S)-2-(2,4-difluorophenyl)oxiranyl]propyl tetrahydro-2H-pyran-2-yl ether; 2-([(2S)-2-[(2S)-2-(2,4-difluorophenyl)oxiranyl]propyl]oxy)tetrahydro-2H-pyran 【CA登记号】 |
【 分 子 式 】C16H20F2O3 【 分 子 量 】298.3298064 【元素组成】C 64.42% H 6.76% F 12.74% O 16.09% |
合成路线1
该中间体在本合成路线中的序号：(V)The nitrile (III), a chiral key intermediate of this synthesis, can be obtained by two different synthetic routes as follows: Route-a: The key step of this route is ring opening reaction of the trisubstituted oxirane (VII) by cyanide anion leading to the nitrile (III). The chiral oxirane (VII) is synthesized from (R)-lactic acid derivatives as already reported. The reaction of (VII) with diethylaluminum cyanide in toluene or lithium cyanide in tetrahydrofuran gives the nitrile (III) with high yield without any epimerization reaction.
| 【1】 Saji, I.; Tamoto, K.; Tanaka, Y.; Fujimoto, K.; Ohashi, N.; Stereoselective synthesis of antifungal agent threo-2-(2,4-difluorophenyl)-3-methylsulfonyl-1-(1H-1,2,4-triazol-1-yl)-2-butanol (SM-8668). Bull Chem Soc Jpn 1994, 67, 1427-33. |
| 【2】 Konos, T.; Miyaoka, T.; Tajima, Y.; Oida, S.; Triazole antifungals. III. Stereocontrolled synthesis of an optically active triazolylmethyloxirane precursor to antifungal oxazolodine derivatives. Chem Pharm Bull 1991, 39, 9, 2241. |
| 【3】 Naito, T.; Hata, K.; Tsuruoka, A.; ER-30346. Drugs Fut 1996, 21, 1, 20. |
| 【4】 Tasaka, A.; Tamura, N.; Matsushita, Y.; Teranishi, K.; Hayashi, R.; Okonogi, K.; Itoh, K.; Optically active antifungal azoles. I. Synthesis and antifungal activity of (2R,3R)-2-(2,4-difluorophenyl)-3-mercapto-1-(1H-1,2,4-triazol-1-yl)-2-butanol and stereoisomers. Chem Pharm Bull 1993, 41, 6, 1035-42. |
| 【5】 Naito, T.; Hata, K.; Kaku, Y.; Tsuruoka, A.; Tsukada, I.; Yanagisawa, M.; Toyosawa, T.; Nara, K. (Eisai Co., Ltd.); Azole antifungal agents, process for the preparation thereof and intermediates. CA 2141731; EP 0667346; JP 1995223950; JP 1996020578; JP 1996053426; US 5648372; US 5789429; US 5792781 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (III) | 17123 | (2S,3R)-3-(2,4-difluorophenyl)-3-hydroxy-2-methyl-4-(1H-1,2,4-triazol-1-yl)butanenitrile | C13H12F2N4O | 详情 | 详情 | |
| (IV) | 13100 | (2R)-1-(2,4-Difluorophenyl)-2-hydroxy-1-propanone | C9H8F2O2 | 详情 | 详情 | |
| (V) | 17125 | (2S)-2-[(2S)-2-(2,4-difluorophenyl)oxiranyl]propyl tetrahydro-2H-pyran-2-yl ether; 2-([(2S)-2-[(2S)-2-(2,4-difluorophenyl)oxiranyl]propyl]oxy)tetrahydro-2H-pyran | C16H20F2O3 | 详情 | 详情 | |
| (VI) | 13106 | (2R,3R)-2-(2,4-Difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2,3-butanediol | C12H13F2N3O2 | 详情 | 详情 | |
| (VII) | 13114 | 1-[[(2S,3S)-2-(2,4-Difluorophenyl)-3-methyloxiranyl]methyl]-1H-1,2,4-triazole | C12H11F2N3O | 详情 | 详情 |