【结 构 式】 |
【分子编号】50851 【品名】butyl 7-[(3R)-3-hydroxy-5-oxo-1-cyclopenten-1-yl]heptanoate 【CA登记号】 |
【 分 子 式 】C16H26O4 【 分 子 量 】282.38004 【元素组成】C 68.06% H 9.28% O 22.66% |
合成路线1
该中间体在本合成路线中的序号:(VII)Treatment of (1E,3S)-1-iodo-3-(tert-butyldimethylsilyloxy)-1-octene (I) with BuLi in ethyl ether, followed by reaction with 7-[3(R)-(tert-butyldimethylsilyloxy)-5-oxo-1-cyclopenten-1-yl] heptanoic acid butyl ester (II) by means of tributylphosphine-copper(I) iodide complex and tributylphosphine in ethyl ether provides the protected nonisolated intermediate (III), which is treated with butyric anhydride (IV) to afford derivative (V). Finally, this compound is converted into the desired product by removal of the TBDMS groups by means HF in acetonitrile/H2O (1). Alternatively, the synthesis can be performed by following a different protection strategy: Esterification of carboxylic acid (VI) with butyl iodide in DMSO by means of diisopropylamine provides derivative (VII), which is then protected by reaction with 3,4-dihydro-2H-pyran (VIII) to furnish compound (IX). Next, coupling of (IX) with iodo derivative (I) by means of tert-BuLi, tributylphosphine - copper (I) iodide complex and tributylphosphine in ethyl ether gives the adduct (X), which by reaction with butyric anhydride (IV) affords derivative (XI). Finally, this compound is converted into the desired product by following this deprotection protocol: 1) Bu4NF in THF; 2) Ac2O, DMAP in CH2Cl2 in the presence of pyridine; and finally 3) pyridinium p-toluenesulfonate (PPTS) in EtOH.
【1】 Makino, M.; et al.; Synthesis of novel prostaglandin E1 prodrugs as inhibitors of platelet aggregation. Reports Res Lab Asahi Glass Co Ltd 1997, 47, 95. |
【2】 Mizushima, Y.; Inomata, T.; Yasuda, A. (Asahi Glass Co., Ltd.; Seikagaku Corp.); Emulsion of lipid containing a prostaglandin analogue. EP 0423697; EP 0624574 . |
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) | 50846 | tert-butyl(dimethyl)silyl (1S,2E)-3-iodo-1-pentyl-2-propenyl ether; tert-butyl[[(1S,2E)-3-iodo-1-pentyl-2-propenyl]oxy]dimethylsilane | C14H29IOSi | 详情 | 详情 | |
(II) | 50847 | butyl 7-((3R)-3-[[tert-butyl(dimethyl)silyl]oxy]-5-oxo-1-cyclopenten-1-yl)heptanoate | C22H40O4Si | 详情 | 详情 | |
(III) | 50848 | butyl 7-[(4R,5R)-4-[[tert-butyl(dimethyl)silyl]oxy]-5-((E,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-1-octenyl)-2-hydroxy-1-cyclopenten-1-yl]heptanoate | C36H70O5Si2 | 详情 | 详情 | |
(IV) | 25047 | butyric anhydride | 106-31-0 | C8H14O3 | 详情 | 详情 |
(V) | 50849 | butyl 7-[(4R,5R)-4-[[tert-butyl(dimethyl)silyl]oxy]-5-((E,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-1-octenyl)-2-(butyryloxy)-1-cyclopenten-1-yl]heptanoate | C40H76O6Si2 | 详情 | 详情 | |
(VI) | 50850 | 7-[(3R)-3-hydroxy-5-oxo-1-cyclopenten-1-yl]heptanoic acid | C12H18O4 | 详情 | 详情 | |
(VII) | 50851 | butyl 7-[(3R)-3-hydroxy-5-oxo-1-cyclopenten-1-yl]heptanoate | C16H26O4 | 详情 | 详情 | |
(VIII) | 13684 | 3,4-Dihydro-2H-pyran;2,3-Dihydro-4H-pyran; 5,6-Dihydro-4H-pyran;Dihydropyran | 110-87-2 | C5H8O | 详情 | 详情 |
(IX) | 50852 | butyl 7-[(3R)-5-oxo-3-(tetrahydro-2H-pyran-2-yloxy)-1-cyclopenten-1-yl]heptanoate | C21H34O5 | 详情 | 详情 | |
(X) | 50853 | butyl 7-[(2R,3R)-2-((E,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-1-octenyl)-5-oxo-3-(tetrahydro-2H-pyran-2-yloxy)cyclopentyl]heptanoate | C35H64O6Si | 详情 | 详情 | |
(XI) | 50854 | butyl 7-[(4R,5R)-5-((E,3S)-3-[[tert-butyl(dimethyl)silyl]oxy]-1-octenyl)-2-(butyryloxy)-4-(tetrahydro-2H-pyran-2-yloxy)-1-cyclopenten-1-yl]heptanoate | C39H70O7Si | 详情 | 详情 |