N-(3-acetyl-4-hydroxyphenyl)acetamide -Drug Synthesis Database

【结构式】

【分子编号】21612

【品名】N-(3-acetyl-4-hydroxyphenyl)acetamide

【CA登记号】

【分子式】C₁₀H₁₁NO₃

【分子量】193.20228

【元素组成】C 62.17% H 5.74% N 7.25% O 24.84%

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：(II)

Friedel-Crafts acetylation of acetaminophen (I) using acetyl chloride and AlCl3 gave acetophenone (II). Subsequent condensation of (II) with N-(tert-butoxycarbonyl)-4-piperidone (III) in the presence of pyrrolidine provided the spirochroman-2,4'-piperidine (IV), from which the diamine (V) was obtained by acid hydrolysis. The piperidine amino group of (VI) was then alkylated with 1-(2-bromoethyl)naphthalene (VI) to afford (VII). Finally, condensation of the remaining amino group of (VII) with the sulfonyl chloride (VIII) furnished the title sulfonamide.

参考文献中间体

合成目标

【1】 Nerenberg, J.B.; et al.; 4-Oxospiro[benzopyran-2,4'-piperidines] as selective alpha1a-adrenergic receptor antagonists. Bioorg Med Chem Lett 1999, 9, 2, 291.

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)	21611	4'-Hydroxyacetanilide;4-Acetamidophenol;N-Acetyl-4-aminophenol;Paracetamol;Acetaminophen;p-Hydroxyacetanilide; Paracetamol; N-(4-hydroxyphenyl)acetamide	103-90-2	C₈H₉NO₂	详情	详情
(II)	21612	N-(3-acetyl-4-hydroxyphenyl)acetamide		C₁₀H₁₁NO₃	详情	详情
(III)	18620	tert-butyl 4-oxo-1-piperidinecarboxylate;BOC-Piperidone;N-(tert-Butoxycarbonyl)-4-piperidone; N-Boc-4-piperidone	79099-07-3	C₁₀H₁₇NO₃	详情	详情
(IV)	21614	6-Aceatmido-4-oxo-3,4-dihydro-2H-spiro[1-benzopyran-2,4'-piperidin]-1'-ylcarboxylic acid tert-butyl ester		C₂₀H₂₆N₂O₅	详情	详情
(V)	21615	6-Amino-3,4-dihydro-2H-spiro[1-benzopyran-2,4'-piperidin]-4-one		C₁₃H₁₆N₂O₂	详情	详情
(VI)	21616	1-(2-bromoethyl)naphthalene	13686-49-2	C₁₂H₁₁Br	详情	详情
(VII)	21617	6-Amino-1'-[2-(1-naphthyl)ethyl]-3,4-dihydro-2H-spiro[1-benzopyran-2,4'-piperidin]-4-one		C₂₅H₂₆N₂O₂	详情	详情
(VIII)	21618	3,5-dimethyl-4-isoxazolesulfonyl chloride	80466-79-1	C₅H₆ClNO₃S	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 acetylation of 4-acetamidophenol (I) with acetyl chloride in refluxing benzene gives 4-acetoxyacetanilide (II), which by a Fries reaction with AlCl3 at 170 C is converted into 2-hydroxy-5-acetamidoacetophenone (III). (1,2) The reaction of (III) with epichlorohydrin (IV) by means of sodium ethoxide in refluxing ethanol affords 1-(2-acetyl-4-acetamidophenoxy)-2,3-epoxypropane (V), which is finally treated with isopropylamine (VI) in refluxing ethanol. (1-3)

参考文献中间体

合成目标

【1】 Woolbridge, K.R.H.; Basil, B (May & Baker, Ltd.); ZA 6808345 .
【2】 Basil, B.; et al.; New series of cardioselective adrenergic beta-receptor blocking compounds. 1-(2-Acyl-4-acylaminophenoxy)3-isopropylaminopropan-2-ols. J Med Chem 1976, 19, 3, 399.
【3】 Woolbridge, K.R.H.; Basil, B. (May & Baker, Ltd.); BE 715205; CA 834734; CH 485663; CH 489467; FR 1570087; FR M7616; GB 1231783; GB 681537; JP 7134414; NL 6806946; ZA 6803130 .
【4】 Blancafort, P.; Serradell, M.N.; Castaner, J.; Weetman, D.F.; Diacetolol hydrochloride. Drugs Fut 1981, 6, 8, 467.

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)	21611	4'-Hydroxyacetanilide;4-Acetamidophenol;N-Acetyl-4-aminophenol;Paracetamol;Acetaminophen;p-Hydroxyacetanilide; Paracetamol; N-(4-hydroxyphenyl)acetamide	103-90-2	C₈H₉NO₂	详情	详情
(II)	60980	4-(acetylamino)phenyl acetate		C₁₀H₁₁NO₃	详情	详情
(III)	21612	N-(3-acetyl-4-hydroxyphenyl)acetamide		C₁₀H₁₁NO₃	详情	详情
(IV)	10146	Epichlorohydrin; 2-(Chloromethyl)oxirane	106-89-8	C₃H₅ClO	详情	详情
(V)	60981	N-[3-acetyl-4-(2-oxiranylmethoxy)phenyl]acetamide		C₁₃H₁₅NO₄	详情	详情
(VI)	23933	2-Propanamine; Isopropylamine	75-31-0	C₃H₉N	详情	详情

Extended Information