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【结 构 式】

【分子编号】15441

【品名】tert-butyl (5R)-6-cyano-5-hydroxy-3-oxohexanoate

【CA登记号】

【 分 子 式 】C11H17NO4

【 分 子 量 】227.26032

【元素组成】C 58.14% H 7.54% N 6.16% O 28.16%

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:(XXXIX)

5) The hydrolysis of methyl (Et or Bu) 3(R)-(tert-butyldimethylsilyloxy)-4-cyanobutyrate (XXV) with NaOH gives the corresponding free acid (XXXVI), which is condensed with malonic acid mono-tert-butyl ester magnesium salt (XXXVII) by means of carbonyldiimidazole (CDI) yielding tert-butyl 5(R)-(tert-butyldimethylsilyloxy)-6-cyano-3-oxohexanoate (XXXVIII). The desilylation of (XXXVIII) with tetrabutylammonium fluoride in acetic acid affords the expected hydroxylated ketoester (XXXIX), which is reduced with diethylmethoxyborane and NaBH4 in methanol giving tert-butyl 6-cyano-3(R),5(R)-dihydroxyhexanoate (XL). The protection of the two OH groups of (XL) with acetone dimethylketal (XXIX) and methanesulfonic acid affords the 1,3-dioxane (XLI) (6), which by reduction of its CN group by hydrogenation with H2 over Pd/C gives intermediate (4R,6R)-2-[6-(2-aminoethyl)-2,2-dimethyl-1,3-dioxan-4-yl]acetic acid tert-butyl ester (XLII). 6) The (4R,6R)-2-[6-(cyanomethyl)-2,2-dimethyl-1,3-dioxan-4-yl]acetic acid tert-butyl ester (XLI) can also be obtained by reaction of (4R,6R)-2-[6-(2-hydroxyethyl)-2,2-dimethyl-1,3-dioxan-4-yl]acetic acid tert-butyl ester (XLVIII) with tosyl chloride to give the corresponding tosylate (XVIX), which is then treated with NaCN. 7) The tert-butyl 6-cyano-5(R)-hydroxy-3-oxohexanoate (XXXIX) can also be obtained by condensation of methyl 4-cyano-3(R)-hydroxybutyrate (L) with tert-butyl acetate (XXIII) by means of LDA in THF.

1 Graul, A.; Castaner, J.; Atorvastatin Calcium. Drugs Fut 1997, 22, 9, 956.
2 Roth, B.D.; Baumann, K.L.; Butler, D.E.; Deering, C.F.; Mennen, K.E.; Millar, A.; Nanninga, T.N.; Palmer, C.W.; The convergent synthesis of CI-981, an optically active, highly potent, tissue selective inhibitor of HMG-CoA reductase. Tetrahedron Lett 1992, 33, 17, 2283-4.
3 Brower, P.L.; Butler, D.E.; Deering, C.F.; Le, T.V.; Millar, A.; Nanninga, T.N.; Roth, B.D.; The synthesis of (4R-cis)-1,1-dimethylethyl 6-cyanomethyl-2,2-dimethyl-1,3-dioxane-4-acetate, a key intermediate for the preparation of CI-981, a highly potent, tissue selective inhibitor of HMG-CoA reductase. Tetrahedron Lett 1992, 33, 17, 2279-82.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XXIII) 15097 7-[(2-aminopropyl)amino]-1-cyclopropyl-6-fluoro-5-methyl-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid C17H20FN3O3 详情 详情
(XXIX) 10722 1-Methoxy-1-methylethyl methyl ether; 2,2-Dimethoxypropane 77-76-9 C5H12O2 详情 详情
(XXXV) 15437 methyl (3R)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-cyanobutanoate C12H23NO3Si 详情 详情
(XXXVI) 15438 (3R)-3-[[tert-butyl(dimethyl)silyl]oxy]-4-cyanobutyric acid C11H21NO3Si 详情 详情
(XXXVII) 15439 Bis(malonic acid mono-tert-butyl ester)magnesium salt C14H22MgO8 详情 详情
(XXXVIII) 15440 tert-butyl (5R)-5-[[tert-butyl(dimethyl)silyl]oxy]-6-cyano-3-oxohexanoate C17H31NO4Si 详情 详情
(XXXIX) 15441 tert-butyl (5R)-6-cyano-5-hydroxy-3-oxohexanoate C11H17NO4 详情 详情
(XL) 15442 tert-butyl (3R,5R)-6-cyano-3,5-dihydroxyhexanoate C11H19NO4 详情 详情
(XLI) 15443 tert-Butyl (4R,3R)-6-cyanomethyl-2,2-dimethyl-1,3-dioxane-4-acetate;tert-butyl 2-[(4R,6R)-6-(cyanomethyl)-2,2-dimethyl-1,3-dioxan-4-yl]acetate 125971-94-0 C14H23NO4 详情 详情
(XLII) 15444 (4R,6R)-tert-Butyl-6-(2-aminoethyl)-2,2-dimethyl-1,3-dioxane-4-acetate; (4R-Cis)-1,1-Dimethylethyl-6-aminoethyl-2,2-dimethyl-1,3-dioxoane-4-acetate 125995-13-3 C14H27NO4 详情 详情
(XLVIII) 15445 tert-butyl 2-[(4R,6S)-6-(hydroxymethyl)-2,2-dimethyl-1,3-dioxan-4-yl]acetate 124655-09-0 C13H24O5 详情 详情
(XLIX) 15446 tert-butyl 2-[(4R,6S)-2,2-dimethyl-6-([[(4-methylphenyl)sulfonyl]oxy]methyl)-1,3-dioxan-4-yl]acetate C20H30O7S 详情 详情
(L) 15447 methyl (5R)-6-cyano-5-hydroxy-3-oxohexanoate C8H11NO4 详情 详情
Extended Information