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【结 构 式】

【分子编号】64732

【品名】3-(5-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-3-hydroxy-2,4-dimethylpentanoyl)-4-(phenylmethyl)-1,3-oxazolidin-2-one

【CA登记号】

【 分 子 式 】C23H37NO5Si

【 分 子 量 】435.63602

【元素组成】C 63.41% H 8.56% N 3.22% O 18.36% Si 6.45%

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:(IV)

Protection of (S)-3-hydroxy-2-methylpropionic acid methyl ester (I) as the corresponding silyl ether, followed by reduction with DIBAL provides the aldehyde (II). Diastereoselective aldol condensation of (II) with the chiral N-propionyl oxazolidinone (III) in the presence of dibutylboron triflate leads to adduct (IV), which is then reduced with LiBH4 to give the diol (V). The diol (V) is protected as the cyclic ketal (VII) by treatment with anisaldehyde dimethylacetal (VI) in the presence of pyridinium p-toluenesulfonate (PPTS). Desilylation of (VII) using tetrabutylammonium fluoride yields the alcohol (VIII). Subsequent iodination of (VIII) with I2/PPh3, followed by displacement of alkyl iodide (IX) with PPh3 in refluxing benzene, furnishes the phosphonium salt (X).

1 Choy, N.; Shin, Y.; Nguyen, P.Q.; Curran, D.P.; Balachandran, R.; Madiraju, C.; Day, B.W.; Simplified discodermolide analogues: Synthesis and biological evaluation of 4-epi-7-dehydroxy-14,16-didemethyl-(+)-discodermolides as microtubule-stabilizing agents. J Med Chem 2003, 46, 14, 2846.
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) 17128 Methyl (2S)-3-hydroxy-2-methylpropanoate 72657-23-9 C5H10O3 详情 详情
(II) 42624 (2S)-3-[[tert-butyl(dimethyl)silyl]oxy]-2-methylpropanal C10H22O2Si 详情 详情
(III) 25713 (4S)-4-benzyl-3-propionyl-1,3-oxazolidin-2-one C13H15NO3 详情 详情
(IV) 64732 3-(5-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-3-hydroxy-2,4-dimethylpentanoyl)-4-(phenylmethyl)-1,3-oxazolidin-2-one C23H37NO5Si 详情 详情
(V) 64733 5-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-2,4-dimethyl-1,3-pentanediol C13H30O3Si 详情 详情
(VI) 26485 1-(dimethoxymethyl)-4-methoxybenzene 2186-92-7 C10H14O3 详情 详情
(VII) 64734 (1,1-dimethylethyl)(dimethyl)[(2-{5-methyl-2-[4-(methyloxy)phenyl]-1,3-dioxan-4-yl}propyl)oxy]silane; (1,1-dimethylethyl)(dimethyl)silyl 2-{5-methyl-2-[4-(methyloxy)phenyl]-1,3-dioxan-4-yl}propyl ether C21H36O4Si 详情 详情
(VIII) 64735 2-{5-methyl-2-[4-(methyloxy)phenyl]-1,3-dioxan-4-yl}-1-propanol C15H22O4 详情 详情
(IX) 64736 4-(2-iodo-1-methylethyl)-5-methyl-2-[4-(methyloxy)phenyl]-1,3-dioxane; 4-[4-(2-iodo-1-methylethyl)-5-methyl-1,3-dioxan-2-yl]phenyl methyl ether C15H21IO3 详情 详情
(X) 64737 (2-{5-methyl-2-[4-(methyloxy)phenyl]-1,3-dioxan-4-yl}propyl)(triphenyl)phosphonium iodide C33H36IO3P 详情 详情
Extended Information