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【结 构 式】 
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【分子编号】59957 【品名】(1R)-1-[(2R)-2-(2,4-difluorophenyl)oxiranyl]ethyl methanesulfonate 【CA登记号】 |
【 分 子 式 】C11H12F2O4S 【 分 子 量 】278.2766864 【元素组成】C 47.48% H 4.35% F 13.65% O 23% S 11.52% |
合成路线1
该中间体在本合成路线中的序号：(XXXIII)2) Propiophenone derivative (XXV) - prepared according to a procedure similar to that described for compound (XIX) - is subjected to a Grignard reaction with (chloromethyl)trimethylsilane (XXVI) and Mg in ether to give the silyl alcohol (XXVII), which by treatment with p-toluenesulfonic acid in MeOH undergoes b-elimination and deprotection to yield the allylic alcohol (XXVIII). Epoxidation of (XXVIII) with tert-butyl hydroperoxide and catalytic oxyvanadium acetylacetonate gives the epoxy-alcohol (XXIX), which is subjected to a Mitsunobu reaction with benzoic acid (XXX) by means of DEAD and PPh3 in THF to provide benzoate (XXXI). Solvolysis of compound (XXXI) in MeOH with catalytic NaOMe yields the epoxyalcohol (XXXII), which is mesylated with methanesulfonyl chloride and triethylamine in CH2Cl2 to afford the protected alcohol (XXXIII). Finally, treatment of compound (XXXIII) with 1H-1,2,4-triazole (XXIV) and NaH in DMF affords the desired intermediate (IX).
| 【1】 Sorbera, L.A.; del Fresno, M.; Rabasseda, X.; CS-758. Drugs Fut 2003, 28, 3, 217. |
| 【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. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IX) | 31738 | 1-[[(2R,3S)-2-(2,4-difluorophenyl)-3-methyloxiranyl]methyl]-1H-1,2,4-triazole | C12H11F2N3O | 详情 | 详情 | |
| (XIV) | 13135 | 1H-1,2,4-Triazole; 1,2,4-Triazole | 288-88-0 | C2H3N3 | 详情 | 详情 |
| (XXV) | 43511 | (2S)-1-(2,4-difluorophenyl)-2-(tetrahydro-2H-pyran-2-yloxy)-1-propanone | C14H16F2O3 | 详情 | 详情 | |
| (XXVI) | 59954 | (chloromethyl)(trimethyl)silane | C4H11ClSi | 详情 | 详情 | |
| (XXVII) | 59955 | (3S)-2-(2,4-difluorophenyl)-3-(tetrahydro-2H-pyran-2-yloxy)-1-(trimethylsilyl)-2-butanol | C18H28F2O3Si | 详情 | 详情 | |
| (XXVIII) | 59956 | (2S)-3-(2,4-difluorophenyl)-3-buten-2-ol | C10H10F2O | 详情 | 详情 | |
| (XXIX) | 27877 | (1S)-1-[(2R)-2-(2,4-difluorophenyl)oxiranyl]-1-ethanol | C10H10F2O2 | 详情 | 详情 | |
| (XXX) | 10202 | Benzoic acid | 65-85-0 | C7H6O2 | 详情 | 详情 |
| (XXXI) | 43518 | (1S)-1-[(2S)-2-(2,4-difluorophenyl)oxiranyl]ethyl benzoate | C17H14F2O3 | 详情 | 详情 | |
| (XXXII) | 27875 | (1R)-1-[(2R)-2-(2,4-difluorophenyl)oxiranyl]-1-ethanol | C10H10F2O2 | 详情 | 详情 | |
| (XXXIII) | 59957 | (1R)-1-[(2R)-2-(2,4-difluorophenyl)oxiranyl]ethyl methanesulfonate | C11H12F2O4S | 详情 | 详情 |