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【结 构 式】 
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【分子编号】22675 【品名】allyl 3-oxobutanoate 【CA登记号】1118-84-9 |
【 分 子 式 】C7H10O3 【 分 子 量 】142.1546 【元素组成】C 59.14% H 7.09% O 33.76% |
合成路线1
该中间体在本合成路线中的序号：(III)1) The trans-esterification of methyl acetoacetate (I) with allyl alcohol (II) gives the allyl ester (III), which is treated with p-toluenesulfonyl azide (IV) and triethylamine in acetonitrile to yield the diazo derivative (V). The reaction of (V) with tert-butyl-dimethylsilyl triflate (VI) and triethyl amine in dichloromethane affords the enol silyl ether (VII), which is condensed with 3-[1-(tert-butyldimethyl-silyloxy)ethyl-4 acetoxyazetidin-2-one (VIII) by means of ZnCl2 in dichloromethane giving 3-[l-(tertbutyldimethylsilyloxy)ethyl]-4-(4-allyloxy-3-diazo-2,4-dioxobutyl)azetidin-2-one (IX). The cyclization of (IX) by means of rhodium acetate in refluxing benzene yields allyl 6alpha-[l(R)-hydroxyethyl]-2-oxocarbapenam-3-carboxylate (X), which is condensed with 2-(mercaptomethyl)pyridine (XI) by means of diphenyl chlorophosphate and diisopropylamine in acetonitrile affording allyl 6alpha-[l(R)-hydroxy-ethyl]-2-(2-pyridylmethylthio)carbapen-2-em-3-carboxylate (XII). The hydrolysis of (XII) with tetrakis-triphenylphosphine-palladium, triphenylphosphine and potassium 2-ethylhexanoate in dichloromethane gives the potassium salt (XIII), which is finally quaternized with methyl triflate and p-toluenesulfonic acid in acetone.
| 【1】 Kim, C.U. (Bristol-Myers Squibb Co.); Carbapenem antibiotics. DE 3334937; GB 2128187; US 4644061 . |
| 【2】 Prous, J.; Castaner, J.; BMY-25174. Drugs Fut 1988, 13, 6, 511. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 11791 | methyl 3-oxobutanoate; Methyl acetoacetate | 105-45-3 | C5H8O3 | 详情 | 详情 |
| (II) | 12234 | 2-Propen-1-ol; Allyl alcohol | 107-18-6 | C3H6O | 详情 | 详情 |
| (III) | 22675 | allyl 3-oxobutanoate | 1118-84-9 | C7H10O3 | 详情 | 详情 |
| (IV) | 22676 | p-Toluenesulfonyloxy azide | C7H7N3O3S | 详情 | 详情 | |
| (V) | 22677 | 2-Diazo-3-oxobutyric acid allyl ester | C7H8N2O3 | 详情 | 详情 | |
| (VI) | 22678 | tert-butyl(dimethyl)silyl trifluoromethanesulfonate | 69739-34-0 | C7H15F3O3SSi | 详情 | 详情 |
| (VII) | 22679 | 2-Diazo-3-(tert-butyldimethylsilyloxy)-3-butenoic acid allyl ester | C13H22N2O3Si | 详情 | 详情 | |
| (VIII) | 22680 | (3R)-3-((1R)-1-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-4-oxoazetidinyl acetate | C13H25NO4Si | 详情 | 详情 | |
| (IX) | 22681 | 4-[3(S)-[1(R)-(Tert-butyldimethylsilyloxy)ethyl]-4-oxoazetidin-2(R)-yl]-2-diazo-3-oxobutyric acid allyl ester | C18H29N3O5Si | 详情 | 详情 | |
| (X) | 22682 | allyl (5R,6S)-6-[(1R)-1-hydroxyethyl]-3,7-dioxo-1-azabicyclo[3.2.0]heptane-2-carboxylate | C12H15NO5 | 详情 | 详情 | |
| (XI) | 22683 | 2-pyridinylmethylhydrosulfide; 2-pyridinylmethanethiol | C6H7NS | 详情 | 详情 | |
| (XII) | 22684 | allyl (5R,6S)-6-[(1R)-1-hydroxyethyl]-7-oxo-3-[(2-pyridinylmethyl)sulfanyl]-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate | C18H20N2O4S | 详情 | 详情 | |
| (XIII) | 22685 | (5R,6S)-6-[(1R)-1-hydroxyethyl]-7-oxo-3-[(2-pyridinylmethyl)sulfanyl]-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate | C15H15KN2O4S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(III)Fluorenone-4-carboxaldehyde (II) was obtained by reduction of acid chloride (I). Subsequent Hantzsch synthesis using allyl acetoacetate (III) and ammonium hydroxide in boiling isopropyl alcohol provided the title dihydropyridine.
| 【1】 Valenti, P.; Brudiesi, R.; Rampa, A.; Chiarini, A.; Fluorenone and benzophenone 1,4-dihydropyridine derivatives with cardiodepressant activity. Arzneim-Forsch Drug Res 1992, 42, 11, 1284. |