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【结 构 式】

【分子编号】50852

【品名】butyl 7-[(3R)-5-oxo-3-(tetrahydro-2H-pyran-2-yloxy)-1-cyclopenten-1-yl]heptanoate

【CA登记号】

【 分 子 式 】C21H34O5

【 分 子 量 】366.49796

【元素组成】C 68.82% H 9.35% O 21.83%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(IX)

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
Extended Information