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【结 构 式】

【分子编号】50689

【品名】(1R)-1-[4-(benzyloxy)-3-(2-hydroxyethyl)phenyl]-2-bromo-1-ethanol

【CA登记号】

【 分 子 式 】C17H19BrO3

【 分 子 量 】351.24006

【元素组成】C 58.13% H 5.45% Br 22.75% O 13.67%

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:(XXI)

An alternative method, suitable for large-scale synthesis, has been described: The chloromethylation of 4'-hydroxyacetophenone (XII) using formaldehyde and HCl gave (XIII). Displacement of the chloride group with NaCN provided nitrile (XIV), which was further hydrolyzed to the carboxylic acid (XV). Esterification of (XV) with methanol and sulfuric acid yields (XVI), whose phenolic hydroxyl group was protected as the benzyl ether (XVII) by alkylation with benzyl chloride. Subsequent bromination of ketone (XVII) yielded the phenacyl bromide (XVIII). The chiral amino alcohol (XX) was prepared from (-)-camphor (XIX) by ketone oxidation in position alpha with SeO2, followed by condensation with hydroxylamine and reduction with LiAlH4. Asymmetric reduction of the bromo ketone (XVIII) with borane in the presence of aluminum triethoxide and the chiral auxiliary (XX) provided the desired (R)-bromohydrin (XXI). The hydroxyl groups of (XXI) were then protected by silylation with tert-butyldimethylsilyl chloride, yielding (XXII). Condensation of the silyl-protected bromide (XXII) with (S)-2[(2-amino-1,2,3,4-tetrahydronaphthalen-7-yl)oxy]-N,N-dimethylacetamide (XXIII) furnished adduct (XXIV).

1 Yanagi, T.; et al.; The practical synthesis of a uterine relaxant, bis (2-{[2S)-2-({(2R)-2-hydroxy-2-[4-hydroxy-3-(2-hydroxyethyl)-phenyl]ethyl}amino)-1,2,3,4-tetrahydronaphthalen-7-yl]oxy}-N,N-dimethylacetamide)sulfate (KUR-1246). Chem Pharm Bull 2001, 49, 8, 1018.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(XII) 18123 1-(4-hydroxyphenyl)-1-ethanone; 4'-Hydroxyacetophenone 99-93-4 C8H8O2 详情 详情
(XIII) 39615 1-[3-(chloromethyl)-4-hydroxyphenyl]-1-ethanone C9H9ClO2 详情 详情
(XIV) 50683 2-(5-acetyl-2-hydroxyphenyl)acetonitrile C10H9NO2 详情 详情
(XV) 50684 2-(5-acetyl-2-hydroxyphenyl)acetic acid C10H10O4 详情 详情
(XVI) 50685 methyl 2-(5-acetyl-2-hydroxyphenyl)acetate C11H12O4 详情 详情
(XVII) 50686 methyl 2-[5-acetyl-2-(benzyloxy)phenyl]acetate C18H18O4 详情 详情
(XVIII) 50687 methyl 2-[2-(benzyloxy)-5-(2-bromoacetyl)phenyl]acetate C18H17BrO4 详情 详情
(XIX) 17415 (1R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-one 464-49-3 C10H16O 详情 详情
(XX) 50688 (1R,2S,3R,4S)-3-amino-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol C10H19NO 详情 详情
(XXI) 50689 (1R)-1-[4-(benzyloxy)-3-(2-hydroxyethyl)phenyl]-2-bromo-1-ethanol C17H19BrO3 详情 详情
(XXII) 50690 ([(1R)-1-[4-(benzyloxy)-3-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)phenyl]-2-bromoethyl]oxy)(tert-butyl)dimethylsilane; benzyl 4-((1R)-2-bromo-1-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-2-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)phenyl ether C29H47BrO3Si2 详情 详情
(XXIII) 50691 2-[[(7S)-7-amino-5,6,7,8-tetrahydro-2-naphthalenyl]oxy]-N,N-dimethylacetamide C14H20N2O2 详情 详情
(XXIV) 50692 2-([(7S)-7-[((2R)-2-[4-(benzyloxy)-3-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)phenyl]-2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)amino]-5,6,7,8-tetrahydro-2-naphthalenyl]oxy)-N,N-dimethylacetamide C43H66N2O5Si2 详情 详情
Extended Information