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【结 构 式】

【分子编号】44929

【品名】ethyl (5R)-5-((2S,4R)-4-[(methylsulfonyl)oxy]-1-[[(4-nitrobenzyl)oxy]carbonyl]pyrrolidinyl)-4,5-dihydro-3-isoxazolecarboxylate

【CA登记号】

【 分 子 式 】C19H23N3O10S

【 分 子 量 】485.47184

【元素组成】C 47.01% H 4.78% N 8.66% O 32.96% S 6.61%

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:(XI)

Treatment of trans-4-hydroxy-L-proline (I) with p-nitrobenzyl chloroformate gave the N-protected 4-hydroxyproline (II), which was esterified to afford the N-protected methyl ester (II). Protection of the hydroxyl group of (III) with t-butyl-dimethylsilyl chloride in the presence of imidazole, followed by reduction of the resulting ester (IV) with lithium borohydride, provided the alcohol (V). This was oxidized using pyridine-sulfur trioxide complex to give the formylpyrrolidine (VI). The vinylpyrrolidine (VII) was obtained by Wittig reaction of aldehyde (VI) with methylene triphenylphosphorane. Dipolar cycloaddition of the nitrile oxide resulting from ethyl chlorooximidoacetate (VIII) and Et3N to vinylpyrrolidine (VII) gave iso-oxazolidine (IX) as a mixture of diastereoisomers. After desilylation of (IX) with tetrabutylammonium fluoride, the resulting alcohol (X) was converted into the diastereomeric mixture of mesylates (XI). Chromatographic separation of the required isomer, followed by reduction with LiBH4, yielded alcohol (XII).

1 Park, S.W.; Yoo, K.H.; Shin, K.J.; Kang, Y.K.; Hong, C.Y.; Seo, K.J.; Park, S.Y.; Lee, C.-S.; Kim, D.J.; Synthesis and antibacterial activity of new carbapenems containing isoxazole moiety. Bioorg Med Chem Lett 2000, 10, 2, 95.
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) 14489 (2S,4R)-4-hydroxytetrahydro-1H-pyrrole-2-carboxylic acid; L-Hydroxyproline 51-35-4 C5H9NO3 详情 详情
(II) 22581 (2S,4R)-4-hydroxy-1-[[(4-nitrobenzyl)oxy]carbonyl]-2-pyrrolidinecarboxylic acid C13H14N2O7 详情 详情
(III) 44922 2-methyl 1-(4-nitrobenzyl) (2S,4R)-4-hydroxy-1,2-pyrrolidinedicarboxylate C14H16N2O7 详情 详情
(IV) 44923 2-methyl 1-(4-nitrobenzyl) (2S,4R)-4-[[tert-butyl(dimethyl)silyl]oxy]-1,2-pyrrolidinedicarboxylate C20H30N2O7Si 详情 详情
(V) 44924 4-nitrobenzyl (2S,4R)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-(hydroxymethyl)-1-pyrrolidinecarboxylate C19H30N2O6Si 详情 详情
(VI) 44925 4-nitrobenzyl (2S,4R)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-formyl-1-pyrrolidinecarboxylate C19H28N2O6Si 详情 详情
(VII) 44926 4-nitrobenzyl (2S,4R)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-vinyl-1-pyrrolidinecarboxylate C20H30N2O5Si 详情 详情
(VIII) 30424 2-ethoxy-N-hydroxy-2-oxoethanimidoyl chloride 14337-43-0 C4H6ClNO3 详情 详情
(IX) 44927 ethyl (5R)-5-((2S,4R)-4-[[tert-butyl(dimethyl)silyl]oxy]-1-[[(4-nitrobenzyl)oxy]carbonyl]pyrrolidinyl)-4,5-dihydro-3-isoxazolecarboxylate C24H35N3O8Si 详情 详情
(X) 44928 ethyl (5R)-5-((2S,4R)-4-hydroxy-1-[[(4-nitrobenzyl)oxy]carbonyl]pyrrolidinyl)-4,5-dihydro-3-isoxazolecarboxylate C18H21N3O8 详情 详情
(XI) 44929 ethyl (5R)-5-((2S,4R)-4-[(methylsulfonyl)oxy]-1-[[(4-nitrobenzyl)oxy]carbonyl]pyrrolidinyl)-4,5-dihydro-3-isoxazolecarboxylate C19H23N3O10S 详情 详情
(XII) 44930 4-nitrobenzyl (2S,4R)-2-[(5R)-3-(hydroxymethyl)-4,5-dihydro-5-isoxazolyl]-4-[(methylsulfonyl)oxy]-1-pyrrolidinecarboxylate C17H21N3O9S 详情 详情
Extended Information