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【结 构 式】

【分子编号】22174

【品名】[6-(benzyloxy)hexyl](bromo)magnesium

【CA登记号】

【 分 子 式 】C13H19BrMgO

【 分 子 量 】295.50226

【元素组成】C 52.84% H 6.48% Br 27.04% Mg 8.22% O 5.41%

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:(II)

The Grignard reagent (II), prepared from 6-(benzyloxy)hexyl bromide (I), was condensed with 3-chlorofluoren-9-one (III) to give the carbinol (IV). Hydrogenolysis of (IV) over Pd/C gave fluorenylhexanol (V), which was oxidized to the corresponding aldehyde (VI) under Swern conditions using oxalyl chloride and DMSO. Oxime (VII) was then prepared by reaction of (VI) with hydroxylamine. Treatment of (VII) with NaOCl and Et3N generated an intermediate nitrile oxide which, in the presence of dimethyl itaconate (VIII), experienced a [3+2] cycloaddition to afford the isoxazole (IX). Reductive opening of this heterocycle by hydrogenation in the presence of Raney Nickel and boric acid produced the hydroxyketone (X), and further reduction of (X) using NaHB(OAc)3 in AcOH yielded dihydroxyester (XI) as a mixture of diastereoisomers. Saponification with NaOH, followed by recrystallization of the resulting disodium salt, then furnished the racemic mixture of (3R*,5S*,9R*)- and (3R*,5S*,9S*)-diastereoisomers (XII).

1 Gribble, A.D.; Ife, R.J.; Shaw, A.; McNair, D.; Novelli, C.E.; Bakewell, S.; Shah, V.P.; Dolle, R.E.; Groot, P.H.; Pearce, N.; Yates, J.; Tew, D.; Boyd, H.; Ashman, S.; Eggleston, D.S.; Haltiwanger, R.C.; Okafo, G.; ATP-citrate lyase as a target for hypolipidemic intervention. 2. Synthesis and evaluation of (3R*,5S*)-omega-substituted-3-carboxy-3,5-dihydroxyalkanoic acids and their gamma-lactone prodrugs as inhibitors of the enzyme in vitro and in vivo. J Med Chem 1998, 41, 19, 3582.
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) 22173 1-[[(6-bromohexyl)oxy]methyl]benzene; benzyl 6-bromohexyl ether C13H19BrO 详情 详情
(II) 21416 dimethyl 2-methylenesuccinate 617-52-7 C7H10O4 详情 详情
(II) 22174 [6-(benzyloxy)hexyl](bromo)magnesium C13H19BrMgO 详情 详情
(III) 22175 3-chloro-9H-fluoren-9-one C13H7ClO 详情 详情
(IV) 22176 9-[6-(benzyloxy)hexyl]-3-chloro-9H-fluoren-9-ol C26H27ClO2 详情 详情
(V) 22177 6-(3-chloro-9H-fluoren-9-yl)-1-hexanol C19H21ClO 详情 详情
(VI) 22178 6-(3-chloro-9H-fluoren-9-yl)hexanal C19H19ClO 详情 详情
(VII) 22179 6-(3-chloro-9H-fluoren-9-yl)hexanal oxime C19H20ClNO 详情 详情
(IX) 22181 methyl 3-[5-(3-chloro-9H-fluoren-9-yl)pentyl]-5-(2-methoxy-2-oxoethyl)-4,5-dihydro-5-isoxazolecarboxylate C26H28ClNO5 详情 详情
(X) 22182 dimethyl 2-[7-(3-chloro-9H-fluoren-9-yl)-2-oxoheptyl]-2-hydroxysuccinate C26H29ClO6 详情 详情
(XI) 22183 dimethyl 2-[7-(3-chloro-9H-fluoren-9-yl)-2-hydroxyheptyl]-2-hydroxysuccinate C26H31ClO6 详情 详情
Extended Information