【结 构 式】 |
【分子编号】36372 【品名】methyl (Z)-8-(2,5-dimethoxy-2,5-dihydro-2-furanyl)-5-octenoate 【CA登记号】 |
【 分 子 式 】C15H24O5 【 分 子 量 】284.35256 【元素组成】C 63.36% H 8.51% O 28.13% |
合成路线1
该中间体在本合成路线中的序号:(XIV)The hydrogenation of ethyl 3-(2-furyl)acrylate (I) with H2 over Raney-Ni in ethanol gives ethyl 3-(2-furyl)propionate (II), which oxidative methoxylation with Br2 in methanol affords ethyl 3-(2,5-dimethoxy-2,5-dihydro-2-furyl)propionate (III). The partial reduction of (III) with diisobutylaluminum hydride in toluene yields the substituted propionaldehyde (IV), which by a Wittig condensation with 4-carboxybutyl triphenylphosphonium bromide by means of NaH in DMSO gives 8-(2,5-dimethoxy-2,5-dihydro-2-furyl)-5-octenoic acid (VI). The hydrolytic ring opening of (VI), followed by an aldol cyclization in refluxing dioxane - water by means of sodium acetate - NaH2PO4 - hydroquinone affords 7-(2-oxo-5-hydroxycyclopent-3-en-1-yl)-5-heptenoic acid (VII), which is isomerized by treatment with H2SO4 yielding 7-(5-oxo-3-hydroxycyclopenten-1-yl)-5-heptenoic acid (VIII). Methylation and esterification of (VIII) with H2SO4/refluxing methanol gives the methoxy methyl ester (IX), which by reaction with 2-mercaptoethanol (A) and sodium methoxide in methanol is converted into methyl 7-[5-oxo-3-(2-hydroxyethylthio)cyclopenten-1-yl]-5-heptenoate (X). The methylation of acid (VI) with NaH and methyl iodide gives the corresponding methyl ester (XIV), which is submitted to a hydrolytic ring opening and aldol cyclization as before to afford methyl 7-(2-oxo-5-hydroxycyclopent-3-en-1-yl)-5-heptenoate (XV). The silylation of (XV) with trimethylchlorosilane and hexamethyldisilazane as usual yields the corresponding trimethylsilyloxy derivative (XVI), which is treated with 2-mercaptoethanol (A) and sodium methoxide to give the isomerized compound (X).
【1】 Floyd, M.B.; Prostaglandins and congeners. 18. Synthesis of cyclopentenolone precursors to prostaglandins from 2,5-dihydro-2,5-dimethoxyfurans. J Org Chem 1978, 43, 9, 1641-43. |
【2】 Floyd, M.; et al.; Prostaglandins and congeners. 22. Synthesis of 11-substituted derivatives of 11-deoxyprostaglandins E1 and E2. Potential bronchodilators. J Med Chem 1980, 23, 8, 903-913. |
【3】 Hillier, K.; Serradell, M.N.; Blancafort, P.; Castañer, J.; DHET-PGE2. Drugs Fut 1982, 7, 4, 241. |
【4】 Weiss, M.J.; Siuta, G.J. (American Cyanamid Co.); 11-(2-Hydroxyethylthio)prostenoic acid E{HD 2 {B series derivatives. US 4085272 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(A) | 36375 | 2-Sulfanyl-1-ethanol; 2-Mercaptoethanol | 60-24-2 | C2H6OS | 详情 | 详情 |
(I) | 36362 | ethyl (E)-3-(2-furyl)-2-propenoate | 623-20-1 | C9H10O3 | 详情 | 详情 |
(II) | 36363 | ethyl 3-(2-furyl)propanoate | 10031-90-0 | C9H12O3 | 详情 | 详情 |
(III) | 36364 | ethyl 3-(2,5-dimethoxy-2,5-dihydro-2-furanyl)propanoate | C11H18O5 | 详情 | 详情 | |
(IV) | 36365 | 3-(2,5-dimethoxy-2,5-dihydro-2-furanyl)propanal | C9H14O4 | 详情 | 详情 | |
(V) | 13616 | (4-Carboxybutyl)triphenylphosphonium bromide | 17814-85-6 | C23H24BrO2P | 详情 | 详情 |
(VI) | 36367 | (Z)-8-(2,5-dimethoxy-2,5-dihydro-2-furanyl)-5-octenoic acid | C14H22O5 | 详情 | 详情 | |
(VII) | 36368 | (Z)-7-(2-hydroxy-5-oxo-3-cyclopenten-1-yl)-5-heptenoic acid | C12H16O4 | 详情 | 详情 | |
(VIII) | 36369 | (Z)-7-(3-hydroxy-5-oxo-1-cyclopenten-1-yl)-5-heptenoic acid | C12H16O4 | 详情 | 详情 | |
(IX) | 36370 | methyl (Z)-7-(3-methoxy-5-oxo-1-cyclopenten-1-yl)-5-heptenoate | C14H20O4 | 详情 | 详情 | |
(X) | 36371 | methyl (Z)-7-[3-[(2-hydroxyethyl)sulfanyl]-5-oxo-1-cyclopenten-1-yl]-5-heptenoate | C15H22O4S | 详情 | 详情 | |
(XIV) | 36372 | methyl (Z)-8-(2,5-dimethoxy-2,5-dihydro-2-furanyl)-5-octenoate | C15H24O5 | 详情 | 详情 | |
(XV) | 36373 | methyl (Z)-7-(2-hydroxy-5-oxo-3-cyclopenten-1-yl)-5-heptenoate | C13H18O4 | 详情 | 详情 | |
(XVI) | 36374 | methyl (Z)-7-[2-oxo-5-[(trimethylsilyl)oxy]-3-cyclopenten-1-yl]-5-heptenoate | C16H26O4Si | 详情 | 详情 |