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【结 构 式】 
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【分子编号】52175 【品名】(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl (5R,6S)-6-((1R)-1-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-7-oxo-3-[(2R)tetrahydro-2-furanyl]-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate 【CA登记号】 |
【 分 子 式 】C23H33NO8SSi 【 分 子 量 】511.66846 【元素组成】C 53.99% H 6.5% N 2.74% O 25.02% S 6.27% Si 5.49% |
合成路线1
该中间体在本合成路线中的序号：(XXIX)Treatment of 4-(chloromethyl)-5-methyl-1,3-dioxol-2-one (XXII) with potassium formate (XXIII) by means of KI and NaHCO3 in DMF affords the formyloxymethyl derivative (XXIV), which is converted into the hydroxymethyl derivative (XXV) by refluxing in MeOH. Coupling of compound (XXV) with oxalyl chloride (XXVI) in dichloromethane furnishes compound (XXVII), which is then condensed with protected azetidinone (VI) by means of Et3N in dichloromethane to yield compound (XXVIII). Intramolecular Wittig cyclization of compound (XXVIII) by means of triethyl phosphite in refluxing xylene provides the silylated faropenem daloxate (XXIX), which is finally deprotected by means of either Et3N tris(hydrogen fluoride) in ethyl acetate or tetrabutylammonium fluoride (TBAF) and AcOH in THF.
| 【1】 Rabasseda, X.; Sorbera, L.A.; del Fresno, M.; Castaner, J.; Faropenem daloxate. Drugs Fut 2002, 27, 3, 223. |
| 【2】 Ishiguro, M.; Kanebo, A.; Kaku, T.; Nakatsuka, T. (Nippon Soda Co., Ltd.; Suntory Ltd.); Method of desilylating silylether cpds.. EP 0612749 . |
| 【3】 Fukami, H.; Shima, K.; Nakatsuka, T.; Iwata, H.; Yoshida, T.; Mizukawa, Y.; Shibata, M.; Sekiuchi, K.; Iwanami, T. (Suntory Ltd.); Preparation method of penem derivs.. JP 1994192270 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VI) | 11689 | S-[(2R,3S)-3-((1R)-1-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-4-oxoazetanyl] (2R)tetrahydro-2-furancarbothioate | C16H29NO4SSi | 详情 | 详情 | |
| (XXII) | 16911 | 4-(chloromethyl)-5-methyl-1,3-dioxol-2-one | C5H5ClO3 | 详情 | 详情 | |
| (XXIII) | 52172 | Potassium formate; Formic acid potassium salt | 590-29-4 | CHKO2 | 详情 | 详情 |
| (XXIV) | 50467 | (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl formate | C6H6O5 | 详情 | 详情 | |
| (XXV) | 50468 | 4-(hydroxymethyl)-5-methyl-1,3-dioxol-2-one | C5H6O4 | 详情 | 详情 | |
| (XXVI) | 29841 | Oxalyl chloride; 2-Chloro-2-oxoacetyl chloride | 79-37-8 | C2Cl2O2 | 详情 | 详情 |
| (XXVII) | 52173 | 2-[(5-methyl-2-oxo-1,3-dioxol-4-yl)methoxy]-2-oxoacetyl chloride | C7H5ClO6 | 详情 | 详情 | |
| (XXVIII) | 52174 | (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-((3S,4R)-3-((1R)-1-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-2-oxo-4-[[(2R)tetrahydro-2-furanylcarbonyl]sulfanyl]azetidinyl)-2-oxoacetate | C23H33NO10SSi | 详情 | 详情 | |
| (XXIX) | 52175 | (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl (5R,6S)-6-((1R)-1-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-7-oxo-3-[(2R)tetrahydro-2-furanyl]-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate | C23H33NO8SSi | 详情 | 详情 |