(1R)-2-amino-1-(3,4-bis{[tert-butyl(dimethyl)silyl]oxy}phenyl)-1-ethanol -Drug Synthesis Database

【结构式】

【分子编号】55606

【品名】(1R)-2-amino-1-(3,4-bis{[tert-butyl(dimethyl)silyl]oxy}phenyl)-1-ethanol

【CA登记号】

【分子式】C₂₀H₃₉NO₃Si₂

【分子量】397.7056

【元素组成】C 60.4% H 9.88% N 3.52% O 12.07% Si 14.12%

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：(XIX)

Protection of 3,4-dihydroxybenzaldehyde (XVI) with t-butyldimethylsilyl chloride and imidazole provided the corresponding bis-silyl ether (XVII) (2). Asymmetric nitroaldol condensation of aldehyde (XVII) with nitromethane in the presence of the chiral samarium tris(binaphthoxide) complex (XV) --prepared from (S)-6,6'-bis(trimethylsilylethynyl)-1,1'-dihydroxy-2,2'-binaphthalene (XIV) and samarium triisopropoxide in the presence of BuLi (2,3)-- gave rise to the (R)-nitro alcohol adduct (XVIII) with high optical purity. Catalytic hydrogenation of the nitro group of (XVIII) furnished the silylated norepinephrine (XIX), which was coupled with acid (XIII) in the presence of diethylphosphoryl cyanide to yield amide (XX). Reduction of amide (XX) with LiAlH4 gave amine (XXI). The silyl and methoxymethyl protecting groups were finally removed under acidic conditions to furnish the title compound.

参考文献中间体

合成目标

【1】 Takaoka, E.; et al.; Catalytic asymmetric synthesis of arbutamine. Heterocycles 1997, 46, 157.
【2】 Shibasaki, M.; Fujita, M.; Urata, Y.; Sasai, H. (Chisso Corp.); Optically active nitro alcohol derivs., optically active amino alcohol derivates, and process for preparing the same. EP 0947498; WO 9824753 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XIII)	55601	4-[4-(methoxymethoxy)phenyl]butanoic acid		C₁₂H₁₆O₄	详情	详情
(XIV)	55603			C₃₀H₃₀O₂Si₂	详情	详情
(XV)	55604			C₉₀H₈₄Li₃O₆Si₆Sm	详情	详情
(XVI)	39749	3,4-dihydroxybenzaldehyde	139-85-5	C₇H₆O₃	详情	详情
(XVII)	55602	3,4-bis{[tert-butyl(dimethyl)silyl]oxy}benzaldehyde		C₁₉H₃₄O₃Si₂	详情	详情
(XVIII)	55605	(1R)-1-(3,4-bis{[tert-butyl(dimethyl)silyl]oxy}phenyl)-2-nitro-1-ethanol		C₂₀H₃₇NO₅Si₂	详情	详情
(XIX)	55606	(1R)-2-amino-1-(3,4-bis{[tert-butyl(dimethyl)silyl]oxy}phenyl)-1-ethanol		C₂₀H₃₉NO₃Si₂	详情	详情
(XX)	55607	N-[(2R)-2-(3,4-bis{[tert-butyl(dimethyl)silyl]oxy}phenyl)-2-hydroxyethyl]-4-[4-(methoxymethoxy)phenyl]butanamide		C₃₂H₅₃NO₆Si₂	详情	详情
(XXI)	55608	(1R)-1-(3,4-bis{[tert-butyl(dimethyl)silyl]oxy}phenyl)-2-({4-[4-(methoxymethoxy)phenyl]butyl}amino)-1-ethanol		C₃₂H₅₅NO₅Si₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

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