　 -Drug Synthesis Database

【结构式】

【分子编号】57893

【品名】　

【CA登记号】

【分子式】C₆₄H₆₀O₃Zn₂

【分子量】1007.9586

【元素组成】C 76.26% H 6% O 4.76% Zn 12.97%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(III)

The enantioselective condensation of 4-(tert-butyldimethylsilyloxy)benzaldehyde (I) with nitromethane (II), catalyzed by the chiral Zn ligand complex (III) in THF gives the (R)-2-nitroethanol derivative (IV), which is reduced with H2 over Pd/C in ethanol to yield the 2-aminoethanol derivative (V). The condensation of (V) with carboxylic acid (VI) by means of 2,2-dimethylpropanoyl chloride and DIEA in THF affords the corresponding amide (VII), which is reduced with LiAlH4 in Et2O to yield the protected hydroxyamine (VIII). Finally, this compound is desilylated by means of HCl and KF in MeOH to furnish the target tetrahydroxyamine derivative.

参考文献中间体

合成目标

【1】 Ito, H.; Bremeyer, N.; Trost, B.M.; Yeh, V.S.C.; Effect of ligand structure on the zinc-catalyzed Henry reaction. Asymmetric syntheses of (-)-denopamine and (-)-arbutamine. Org Lett 2002, 4, 16, 2621.

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)	57897	4-{[tert-butyl(dimethyl)silyl]oxy}benzaldehyde		C₁₃H₂₀O₂Si	详情	详情
(II)	39563	nitromethane	75-52-5	CH₃NO₂	详情	详情
(III)	57893			C₆₄H₆₀O₃Zn₂	详情	详情
(IV)	57898	(1R)-1-(4-{[tert-butyl(dimethyl)silyl]oxy}phenyl)-2-nitro-1-ethanol		C₁₄H₂₃NO₄Si	详情	详情
(V)	57899	(1R)-2-amino-1-(4-{[tert-butyl(dimethyl)silyl]oxy}phenyl)-1-ethanol		C₁₄H₂₅NO₂Si	详情	详情
(VI)	24049	2-(3,4-dimethoxyphenyl)acetic acid	93-40-3	C₁₀H₁₂O₄	详情	详情
(VII)	57900	N-[(2R)-2-(4-{[tert-butyl(dimethyl)silyl]oxy}phenyl)-2-hydroxyethyl]-2-(3,4-dimethoxyphenyl)acetamide		C₂₄H₃₅NO₅Si	详情	详情
(VIII)	57901	(1R)-1-(4-{[tert-butyl(dimethyl)silyl]oxy}phenyl)-2-[(3,4-dimethoxyphenethyl)amino]-1-ethanol		C₂₄H₃₇NO₄Si	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

The enantioselective condensation of 3,4-bis(tert-butyldimethylsilyloxy)benzaldehyde (I) with nitromethane (II), catalyzed by the chiral Zn ligand complex (III) in THF gives the (R)-2-nitroethanol derivative (IV), which is reduced with H2 over Pd/C in methanol to yield the 2-aminoethanol derivative (V). The condensation of (V) with 4-[4-(tert-butyldimethylsilyloxy)phenyl]butyric acid (VI) by means of diphenyl chlorophosphate and DIEA in dichloromethane affords the corresponding amide (VII), which is reduced by conventional methods to the protected hydroxyamine (VIII). Finally, this compound is desilylated as usual to furnish the target tetrahydroxyamine derivative.

参考文献中间体

合成目标

【1】 Ito, H.; Bremeyer, N.; Trost, B.M.; Yeh, V.S.C.; Effect of ligand structure on the zinc-catalyzed Henry reaction. Asymmetric syntheses of (-)-denopamine and (-)-arbutamine. Org Lett 2002, 4, 16, 2621.

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)	55602	3,4-bis{[tert-butyl(dimethyl)silyl]oxy}benzaldehyde		C₁₉H₃₄O₃Si₂	详情	详情
(II)	39563	nitromethane	75-52-5	CH₃NO₂	详情	详情
(III)	57893			C₆₄H₆₀O₃Zn₂	详情	详情
(IV)	55605	(1R)-1-(3,4-bis{[tert-butyl(dimethyl)silyl]oxy}phenyl)-2-nitro-1-ethanol		C₂₀H₃₇NO₅Si₂	详情	详情
(V)	55606	(1R)-2-amino-1-(3,4-bis{[tert-butyl(dimethyl)silyl]oxy}phenyl)-1-ethanol		C₂₀H₃₉NO₃Si₂	详情	详情
(VI)	57894	4-(4-{[tert-butyl(dimethyl)silyl]oxy}phenyl)butanoic acid		C₁₆H₂₆O₃Si	详情	详情
(VII)	57895	N-[(2R)-2-(3,4-bis{[tert-butyl(dimethyl)silyl]oxy}phenyl)-2-hydroxyethyl]-4-(4-{[tert-butyl(dimethyl)silyl]oxy}phenyl)butanamide		C₃₆H₆₃NO₅Si₃	详情	详情
(VIII)	57896	(1R)-1-(3,4-bis{[tert-butyl(dimethyl)silyl]oxy}phenyl)-2-{[4-(4-{[tert-butyl(dimethyl)silyl]oxy}phenyl)butyl]amino}-1-ethanol		C₃₆H₆₅NO₄Si₃	详情	详情

Extended Information