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【结 构 式】 
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【分子编号】39689 【品名】3,5-heptanedione 【CA登记号】7424-54-6 |
【 分 子 式 】C7H12O2 【 分 子 量 】128.17108 【元素组成】C 65.6% H 9.44% O 24.97% |
合成路线1
该中间体在本合成路线中的序号：(V)Condensation of 2-chloro-4-methoxyphenol (I) with 1,6-dibromohexane (II) by means of K2CO3 in refluxing acetone to give 1-(2-chloro-4-methoxyphenoxy)-6-bromohexane (III), which is converted into the corresponding iodo derivative (IV) by treatment with NaI in refluxing acetone. Finally, (IV) is treated with the lithium salt of 3,5-heptanedione (V) in ether - DMF.
| 【1】 Collins, J.C.; Diana, G.D.; 3,4-Methylenedioxyphenoxy-alkyl diketones and keto-esters. DE 2435378 . |
| 【2】 Diana, G.D.; et al.; Antiviral acticity of some beta-diketones. 2. Aryloxy alkyl diketones. In vitro activity aganist both RNA and DNA viruses. J Med Chem 1977, 20, 6, 757-761. |
| 【3】 Hopkins, S.J.; Castaner, J.; Arildone. Drugs Fut 1978, 3, 1, 12. |
| 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) | 39686 | 2-chloro-4-methoxyphenol | 18113-03-6 | C7H7ClO2 | 详情 | 详情 |
| (II) | 24786 | 1,6-dibromohexane | 629-03-8 | C6H12Br2 | 详情 | 详情 |
| (III) | 39687 | 6-bromohexyl 2-chloro-4-methoxyphenyl ether; 1-[(6-bromohexyl)oxy]-2-chloro-4-methoxybenzene | C13H18BrClO2 | 详情 | 详情 | |
| (IV) | 39688 | 3-chloro-4-[(6-iodohexyl)oxy]phenyl methyl ether; 2-chloro-1-[(6-iodohexyl)oxy]-4-methoxybenzene | C13H18ClIO2 | 详情 | 详情 | |
| (V) | 39689 | 3,5-heptanedione | 7424-54-6 | C7H12O2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(V)Condensation of the lithium salt of 3,5-heptanedione (V) with 1,6-dibromohexane (II) in DMF giving 4-(6-bromohexyl)-3,5-heptanedione (VI), which is then condensed with 2-chloro-4-methoxyphenol (I) by means of NaH in DMF.
| 【1】 Diana, G.D.; et al.; Antiviral acticity of some beta-diketones. 2. Aryloxy alkyl diketones. In vitro activity aganist both RNA and DNA viruses. J Med Chem 1977, 20, 6, 757-761. |
| 【2】 Hopkins, S.J.; Castaner, J.; Arildone. Drugs Fut 1978, 3, 1, 12. |
合成路线3
该中间体在本合成路线中的序号：(II)Aldol condensation between dimethyl 1,3-acetonedicarboxylate (I) and 3,5-heptanedione (II) produced dimethyl 4,6-diethyl-2-hydroxy-1,3-benzenedicarboxylate (III). After conversion of phenol (III) to the corresponding aryl triflate (IV), Suzuki coupling with 4-fluorobenzeneboronic acid (V) yielded the biphenyl derivative (VI). The diisopropyl compound (VII) was then obtained by methylation of (VI) at the benzylic position using iodomethane and LDA. Partial reduction of diester (VII) with Red-Al?gave rise to the hydroxy ester (VIII), which was further oxidized to aldehyde (IX) by treatment with pyridinium chlorochromate. Wittig reaction of aldehyde (IX) with ethyl triphenylphosphonium bromide furnished the propenyl compound (X)
| 【2】 Schmidt, G.; Wolanin, D.J.; Bischoff, H.; Schoen, W.R.; Angerbauer, R.; Schmidt, D.; Kramss, R.H.; Wohlfeil, S.; Brandes, A.; Muller-Gliemann, M.; Lease, T.G.; Ladouceur, G.H.; Osterhout, M.H.; Hertzog, D.L.; Cook, J.H. II (Bayer AG; Bayer Corp.); Substd. pyridines and biphenyls as anti-hypercholesterinemic, anti-hyperlipoproteinemic and anti-hyperglycemic agents. WO 9804528 . |
| 【1】 Wolanin, D.J.; Schoen, W.R.; Kramss, R.H.; Lease, T.G.; Ladouceur, G.H.; Osterhout, M.H.; Hertzog, D.L.; Cook, J.H. II (Bayer AG; Bayer Corp.); Substd. biphenyls. US 6218431 . |
| 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) | 22692 | dimethyl 3-oxopentanedioate | 1830-54-2 | C7H10O5 | 详情 | 详情 |
| (II) | 39689 | 3,5-heptanedione | 7424-54-6 | C7H12O2 | 详情 | 详情 |
| (III) | 60521 | dimethyl 4,6-diethyl-2-hydroxyisophthalate | C14H18O5 | 详情 | 详情 | |
| (IV) | 60522 | dimethyl 4,6-diethyl-2-{[(trifluoromethyl)sulfonyl]oxy}isophthalate | C15H17F3O7S | 详情 | 详情 | |
| (V) | 38403 | 4-fluorophenylboronic acid | 1765-93-1 | C6H6BFO2 | 详情 | 详情 |
| (VI) | 60523 | dimethyl 3,5-diethyl-4'-fluoro[1,1'-biphenyl]-2,6-dicarboxylate | C20H21FO4 | 详情 | 详情 | |
| (VII) | 60524 | dimethyl 4'-fluoro-3,5-diisopropyl[1,1'-biphenyl]-2,6-dicarboxylate | C22H25FO4 | 详情 | 详情 | |
| (VIII) | 60525 | methyl 4'-fluoro-6-(hydroxymethyl)-3,5-diisopropyl[1,1'-biphenyl]-2-carboxylate | C21H25FO3 | 详情 | 详情 | |
| (IX) | 60526 | methyl 4'-fluoro-6-formyl-3,5-diisopropyl[1,1'-biphenyl]-2-carboxylate | C21H23FO3 | 详情 | 详情 | |
| (X) | 60527 | methyl 4'-fluoro-3,5-diisopropyl-6-[(E)-1-propenyl][1,1'-biphenyl]-2-carboxylate | C23H27FO2 | 详情 | 详情 |