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【结 构 式】 
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【分子编号】29332 【品名】(6E,10E)-3,7,11,15-tetramethyl-6,10,14-hexadecatrienoic acid 【CA登记号】 |
【 分 子 式 】C20H34O2 【 分 子 量 】306.48876 【元素组成】C 78.38% H 11.18% O 10.44% |
合成路线1
该中间体在本合成路线中的序号：(V)The condensation of ethyl cyanoacetate (I) with farnesylacetone (II) by means of acetic acid ammonium acetate in refluxing benzene gives ethyl 2-cyano-3,7,11,15-tetramethyl-6,10,14-hexadecatrienoate (III), which is decarbo-xylated with NaOH in propylene glycol at room temperature yielding 3,7,11,15-tetramethyl-6,10,14-hexadecatrienonitrile (IV). The hydrolysis of (IV) with KOH in propylene glycol water at 130 C affords 3,7,11,15-tetramethyl-6,10,14-hexa-decatrienoic acid (V), which is finally condensed with morpholine (VI) by means of ethyl chlorocarbonate (VII) and triethylamine in THF.
| 【1】 Yamatsu, I.; et al. (Eisai Co., Ltd.); Polyprenylcarboxylic acid amides useful for treating liver dysfunction. BE 0884754; DE 3030462; FR 2463122; FR 2497802; GB 2058782; JP 8126852; JP 8132442; US 4456603 . |
| 【2】 Serradell, M.N.; Castaner, J.; E-0712. Drugs Fut 1985, 10, 5, 387. |
| 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) | 29329 | (5E,9E)-6,10,14-trimethyl-5,9,13-pentadecatrien-2-one | 762-29-8 | C18H30O | 详情 | 详情 |
| (II) | 11877 | Cyanoacetic acid ethyl ester; Ethyl 2-cyanoacetate; Ethyl cyanoacetate; Ethyl isocyanacetate | 105-56-6 | C5H7NO2 | 详情 | 详情 |
| (III) | 29330 | ethyl (6E,10E)-2-cyano-3,7,11,15-tetramethyl-6,10,14-hexadecatrienoate | C23H37NO2 | 详情 | 详情 | |
| (IV) | 29331 | (6E,10E)-3,7,11,15-tetramethyl-6,10,14-hexadecatrienenitrile | C20H33N | 详情 | 详情 | |
| (V) | 29332 | (6E,10E)-3,7,11,15-tetramethyl-6,10,14-hexadecatrienoic acid | C20H34O2 | 详情 | 详情 | |
| (VI) | 10388 | Morpholine | 110-91-8 | C4H9NO | 详情 | 详情 |
| (VII) | 11229 | 1-[(Chlorocarbonyl)oxy]ethane;ethyl carbonochloridate; Carbonchloridic acid ethyl ester;Ethyl chloroformate;Ethyl chlorocarbonate | 541-41-3 | C3H5ClO2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)The alkylation of 4-benzyloxyphenol (I) with 2-(cyclopropylmethoxy)ethyl mesylate (II) by means of NaOCH3 in refluxing methanol gives 4-[2-(cyclopropylmethoxy)-1-ethoxy]phenylmethoxybenzene (III), which is debenzylated by hydrogenolysis with H2 over PdC in methanol yielding 4-[2-(cyclopropylmethoxy)-1-ethoxy]phenol (IV). The treatment of (IV) with epichlorohydrin (V) in aqueous NaOH affords 1-[4-[2-(cyclopropylmethoxy)ethoxyphenoxy]-2,3-epoxy]propane (VI). Finally, this compound is treated with an excess of isopropylamine at room temperature to yield cicloprolol.
| 【1】 Leclerc, G.; Cicloprolol Hydrocloride. Drugs Fut 1985, 10, 12, 975. |
| 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) | 29332 | (6E,10E)-3,7,11,15-tetramethyl-6,10,14-hexadecatrienoic acid | C20H34O2 | 详情 | 详情 | |
| (II) | 18956 | 4-(Benzyloxy)phenol; 4-Benzyloxyphenol | 103-16-2 | C13H12O2 | 详情 | 详情 |
| (III) | 29833 | benzyl 4-[2-(cyclopropylmethoxy)ethoxy]phenyl ether; 1-(benzyloxy)-4-[2-(cyclopropylmethoxy)ethoxy]benzene | C19H22O3 | 详情 | 详情 | |
| (IV) | 29834 | 4-[2-(cyclopropylmethoxy)ethoxy]phenol | C12H16O3 | 详情 | 详情 | |
| (V) | 29776 | 1-(chloromethyl)cyclopropane | 5911-08-0 | C4H7Cl | 详情 | 详情 |
| (VI) | 29835 | 2-([4-[2-(cyclopropylmethoxy)ethoxy]phenoxy]methyl)oxirane; 4-[2-(cyclopropylmethoxy)ethoxy]phenyl 2-oxiranylmethyl ether | C15H20O4 | 详情 | 详情 |