4-[2-[benzyl(tert-butyl)amino]-1-hydroxyethyl]-2-(hydroxymethyl)phenol -Drug Synthesis Database

【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 合成路线2

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.

参考文献中间体

合成目标

【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.

参考文献中间体

合成目标

【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