【结 构 式】 |
【分子编号】21768 【品名】ethyl 2-bromo-2-methylcyclopropanecarboxylate 【CA登记号】 |
【 分 子 式 】C7H11BrO2 【 分 子 量 】207.06714 【元素组成】C 40.6% H 5.35% Br 38.59% O 15.45% |
合成路线1
该中间体在本合成路线中的序号:(XXI)An asymmetric synthesis of the (Z)(R)-enantioner has also been reported. Treatment of bromide (XXI) with NaOEt in Et2O provided ethyl methylenecyclopropanecarboxylate (XXII). Saponification of the ester group of (XXII) afforded racemic acid (XXIII) which, after activation as the mixed anhydride with isobutyl chloroformate, was coupled with (R)-phenylglycinol (XXIV) to yield a mixture of diastereomeric amides (XXV) and (XXVI). Chromatographic separation of the desired (R,R)-diastereoisomer (XXV) was followed by acid hydrolysis to furnish the (R)-acid (XXVII), which was subsequently esterified to (XXVIII) in ethanolic HCl. Addition of Br2 to (XXVIII) produced a mixture of (1S,2S)- and (1S,2R)-dibromoesters (XXIX). Further reduction of (XXIX) to alcohols (XXX) with DIBALH was followed by acetylation with Ac2O in pyridine yielding (XXXI). The alkylation-elimination procedure of the resulting bromides (XXXI) with adenine (V) afforded a mixture of (Z)(R) (XXXII) and (E)(R)- (XXXIII) olefins. Finally, deacetylation with ammonia in MeOH gave a mixture of the target (Z)(R)-compound and the corresponding E-isomer (XXXIV), which were not separed but used for analytical confirmation of the configuration of the title compound.
【1】 Qiu, Y.-L.; et al.; (Z)- and (E)-2-((Hydroxymethyl)cyclopropylidene)methyladenine and -guanine. New nucleoside analogues with a broad-spectrum antiviral activity. J Med Chem 1998, 41, 1, 10. |
【2】 Qiu, Y.-L.; Hempel, A.; Camerman, N.; Camerman, A.; Geiser, F.; Ptak, R.G.; Breitenbach, J.M.; Kira, T.; Li, L.; Gullen, E.; Cheng, Y.C.; Drach, J.C.; Zemlicka, J.; (R)-(-)- and (S)-(+)-synadenol: Synthesis, absolute configuration, and enantioselectivity of antiviral effect. J Med Chem 1998, 41, 26, 5257. |
【3】 Zemilicka, J.; Qiu, Y.-L.; A new efficient synthesis of antiviral methylenecyclopropane analogs of purine nucleosides. Synthesis 1998, 10, 1447-1452. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(XXI) | 21768 | ethyl 2-bromo-2-methylcyclopropanecarboxylate | C7H11BrO2 | 详情 | 详情 | |
(XXII) | 21769 | ethyl 2-methylenecyclopropanecarboxylate | C7H10O2 | 详情 | 详情 | |
(XXIII) | 21770 | 2-methylenecyclopropanecarboxylic acid | C5H6O2 | 详情 | 详情 | |
(XXIV) | 14576 | pentanimidamide | 109-51-3 | C5H12N2 | 详情 | 详情 |
(XXV) | 21772 | (1R)-N-[(1R)-2-hydroxy-1-phenylethyl]-2-methylenecyclopropanecarboxamide | C13H15NO2 | 详情 | 详情 | |
(XXVI) | 21773 | (1S)-N-[(1R)-2-hydroxy-1-phenylethyl]-2-methylenecyclopropanecarboxamide | C13H15NO2 | 详情 | 详情 | |
(XXVII) | 21774 | (1R)-2-methylenecyclopropanecarboxylic acid | C5H6O2 | 详情 | 详情 | |
(XXVIII) | 21775 | ethyl (1R)-2-methylenecyclopropanecarboxylate | C7H10O2 | 详情 | 详情 | |
(XXIX) | 21776 | ethyl (1S)-2-bromo-2-(bromomethyl)cyclopropanecarboxylate | C7H10Br2O2 | 详情 | 详情 | |
(XXX) | 21777 | [(1S)-2-bromo-2-(bromomethyl)cyclopropyl]methanol | C5H8Br2O | 详情 | 详情 | |
(XXXI) | 21778 | [(1S)-2-bromo-2-(bromomethyl)cyclopropyl]methyl acetate | C7H10Br2O2 | 详情 | 详情 | |
(XXXII) | 21779 | [(1R)-2-[(Z)-(6-amino-9H-purin-9-yl)methylidene]cyclopropyl]methyl acetate | C12H13N5O2 | 详情 | 详情 | |
(XXXIII) | 21780 | [(1R)-2-[(E)-(6-amino-9H-purin-9-yl)methylidene]cyclopropyl]methyl acetate | C12H13N5O2 | 详情 | 详情 | |
(XXXIV) | 21781 | [(1R)-2-[(E)-(6-amino-9H-purin-9-yl)methylidene]cyclopropyl]methanol | C10H11N5O | 详情 | 详情 |