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【结 构 式】

【分子编号】39614

【品名】4-[2-[benzyl(tert-butyl)amino]-1-hydroxyethyl]-2-(hydroxymethyl)phenol

【CA登记号】

【 分 子 式 】C20H27NO3

【 分 子 量 】329.43932

【元素组成】C 72.92% H 8.26% N 4.25% O 14.57%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(IV)

The reaction of methyl 5-bromoacetylsalicylate (I) with benzyl tert-butylamine (II) in methyl ethyl ketone gives methyl 5-(N-benzyl-N-tert-butyl-gycyl)salicylate (III), which is reduced with LiAlH4 in refluxing THF yielding alpha'-(N-benzyl-N-tert-butylami-nomethyl)-4-hydroxy-m-xylene-alpha,alpha'-diol (IV). Finally, this compound is debenzylated by hydrogenation with H2 over Pd/C in ethanol-water.

1 Castaner, J.; Blancafort, P.; Serradell, M.N.; Hopkins, S.J.; Albuterol. Drugs Fut 1979, 4, 9, 629.
2 Lunts, L.H.C.; et al.; GB 1200886 .
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) 35836 methyl 5-(2-bromoacetyl)-2-hydroxybenzoate C10H9BrO4 详情 详情
(II) 24700 N-benzyl-2-methyl-2-propanamine 3378-72-1 C11H17N 详情 详情
(III) 39613 methyl 5-[2-[benzyl(tert-butyl)amino]acetyl]-2-hydroxybenzoate C21H25NO4 详情 详情
(IV) 39614 4-[2-[benzyl(tert-butyl)amino]-1-hydroxyethyl]-2-(hydroxymethyl)phenol C20H27NO3 详情 详情

合成路线2

该中间体在本合成路线中的序号:(IV)

The chloromethylation of 4-hydroxyacetophenone (V) with formaldehyde and HCl in hot water gives 3-chloromethyl-4-hydroxyacetophenone (VI), which is treated with acetic anhydride-sodium acetate in refluxing acetic acid to afford 3-acetoxymethyl-4-acetoxyacetophenone (VII). The bromination of (VII) with Br2 in chloroform yields after hydrolysis 3-hydroxymethyl-4-hydroxyphenacyl bromide (VIII), which is condensed with benzyl tert-butylamine (II) in refluxing benzene giving alpha-(N-benzyl-N-tert-butylamino)-4-hydroxy-3-hydroxymethylacetophenone (IX). Finally, this compound is hydrogenated with H2 over Pd/C in ethanol. An alternative method of hydrogenation of (IX) is its reduction with NaBH4 - ethanol, to afford the previously obtained product (IV), which is reduced with H2 over Pd/C in ethanol.

1 Lunts, L.H.C.; et al.; GB 1200886 .
2 Castaner, J.; Blancafort, P.; Serradell, M.N.; Hopkins, S.J.; Albuterol. Drugs Fut 1979, 4, 9, 629.
3 Collin, D.T.; et al.; Saligenin analogs of sympathomimetic catecholamines. J Med Chem 1970, 13, 4, 674-680.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(II) 24700 N-benzyl-2-methyl-2-propanamine 3378-72-1 C11H17N 详情 详情
(IV) 39614 4-[2-[benzyl(tert-butyl)amino]-1-hydroxyethyl]-2-(hydroxymethyl)phenol C20H27NO3 详情 详情
(V) 18123 1-(4-hydroxyphenyl)-1-ethanone; 4'-Hydroxyacetophenone 99-93-4 C8H8O2 详情 详情
(VI) 39615 1-[3-(chloromethyl)-4-hydroxyphenyl]-1-ethanone C9H9ClO2 详情 详情
(VII) 39616 5-acetyl-2-(acetoxy)benzyl acetate C13H14O5 详情 详情
(VIII) 39617 2-bromo-1-[4-hydroxy-3-(hydroxymethyl)phenyl]-1-ethanone C9H9BrO3 详情 详情
(IX) 39618 2-[benzyl(tert-butyl)amino]-1-[4-hydroxy-3-(hydroxymethyl)phenyl]-1-ethanone C20H25NO3 详情 详情
Extended Information