N-(4-hydroxyphenethyl)acetamide -Drug Synthesis Database

【结构式】

【分子编号】19989

【品名】N-(4-hydroxyphenethyl)acetamide

【CA登记号】

【分子式】C₁₀H₁₃NO₂

【分子量】179.21876

【元素组成】C 67.02% H 7.31% N 7.82% O 17.85%

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：(I)

The reaction of 4-[2-(acetylamino)ethyl]phenol (I) with ethyl bromoacetate (II) by means of K2CO3 in refluxing butanone gives 4-[2-(acetylamino)ethyl]phenoxyacetic acid ethyl ester (III), which is hydrolyzed with refluxing aqueous HCl to 4-(2-aminoethyl)phenoxyacetic acid (IV). Finally, this compound is acylated with benzenesulfonyl chloride (V) by means of K2CO3 in hot water.

参考文献中间体

合成目标

【1】 Witte, E.C.; Wolff, H.P.; Thiel, M.; Stegmeier, K.; Roesch, E.; Phenoxyalkylcarboxylic acid compounds and thrombocyte-aggregation inhibition. DE 2809377; EP 0004011; ES 478228; JP 54122250; US 4258058 .
【2】 Karup, G.L.; Preikschat, H.F. (GEA A/S Farmaceutisk Fabrik); Process for the preparation of 1,4-dihydropyridines and cpds. used in this process. WO 9925688 .

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)	19989	N-(4-hydroxyphenethyl)acetamide		C₁₀H₁₃NO₂	详情	详情
(II)	16640	Ethyl 2-bromoacetate; Ethyl bromoacetate	105-36-2	C₄H₇BrO₂	详情	详情
(III)	34332	ethyl 2-[4-[2-(acetamido)ethyl]phenoxy]acetate		C₁₄H₁₉NO₄	详情	详情
(IV)	34333	2-[4-(2-aminoethyl)phenoxy]acetic acid		C₁₀H₁₃NO₃	详情	详情
(V)	14713	benzenesulfonyl chloride	98-09-9	C₆H₅ClO₂S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XI)

1) The N-acylation of DL-serine (I) with 3,5-di-tert-butyl-4-hydroxybenzoic acid by means of carbonyldiimidazole (CDI) in THF gives the acylated serine (III), which is cyclized by means of CBr4/triphenylphosphine/imidazole in acetonitrile to yields the oxazoline (IV). The dehydrogenation of (IV) with activated MnO2 in acetone affords 2-(3,5-di-tert-butyl-4-hydroxyphenyl)oxazole-4-carboxylic acid methyl ester (V), which is reduced with LiBH4 in THF/methanol giving the oxazolylmethnaol (VI). The reaction of (VI) with Br2/triphenylphosphine in acetonitrile yields the bromomethyl derivtive (VII), which is condensed with N-ethyl-N-[2-(4-hydroxyphenyl)ethyl]formamide (VIII) by means of NaH in THF to afford the formylated precursor (IX). Finally, this compound is converted into LY-382924 by reduction of the formyl group with AlH3 (LiAlH4/H2SO4) in THF and treatmnt with HCl gas in CHCl3. 2) The intermediate N-ethyl-N-[2-(4-hydroxyphenyl)ethyl]formamide (VIII) has been obtained as follows: The acylation of 2-(4-hydroxyphenyl)ethylamine (X) with acetic anhydride gives the acetamide (XI), which is reduced with LiAlH4 to the secondary amine (XII). Finally, this amine is formylated with formic acid and carbonyldiimidazole (CDI) in THF.

参考文献中间体

合成目标

【1】 Heinz, L.J.; et al.; Synthesis and biological evaluation of a novel series of antioxidants for the treatment of global cerebral ischemia. 217th ACS Natl Meet (March 21 1999, Anaheim) 1998, Abst MEDI 130.

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)	14224	Serine, methyl ester; methyl 2-amino-3-hydroxypropanoate	2104-89-4	C₄H₉NO₃	详情	详情
(II)	19980	3,5-di(tert-butyl)-4-hydroxybenzoic acid	1421-49-4	C₁₅H₂₂O₃	详情	详情
(III)	19981	methyl 2-[[3,5-di(tert-butyl)-4-hydroxybenzoyl]amino]-3-hydroxypropanoate		C₁₉H₂₉NO₅	详情	详情
(IV)	19982	methyl 2-[3,5-di(tert-butyl)-4-hydroxyphenyl]-4,5-dihydro-1,3-oxazole-4-carboxylate		C₁₉H₂₇NO₄	详情	详情
(V)	19983	methyl 2-[3,5-di(tert-butyl)-4-hydroxyphenyl]-1,3-oxazole-4-carboxylate		C₁₉H₂₅NO₄	详情	详情
(VI)	19984	2,6-di(tert-butyl)-4-[4-(hydroxymethyl)-1,3-oxazol-2-yl]phenol		C₁₈H₂₅NO₃	详情	详情
(VII)	19985	4-[4-(bromomethyl)-1,3-oxazol-2-yl]-2,6-di(tert-butyl)phenol		C₁₈H₂₄BrNO₂	详情	详情
(VIII)	19986	ethyl(4-hydroxyphenethyl)formamide		C₁₁H₁₅NO₂	详情	详情
(IX)	19987	4-([2-[3,5-di(tert-butyl)-4-hydroxyphenyl]-1,3-oxazol-4-yl]methoxy)phenethyl(ethyl)formamide		C₂₉H₃₈N₂O₄	详情	详情
(X)	19988	4-(2-Aminoethyl)phenol; Tyramine	51-67-2	C₈H₁₁NO	详情	详情
(XI)	19989	N-(4-hydroxyphenethyl)acetamide		C₁₀H₁₃NO₂	详情	详情
(XII)	19990	4-[2-(ethylamino)ethyl]phenol		C₁₀H₁₅NO	详情	详情

Extended Information