2-(2-chloroethoxy)acetamide -Drug Synthesis Database

【结构式】

【分子编号】16839

【品名】2-(2-chloroethoxy)acetamide

【CA登记号】

【分子式】C₄H₈ClNO₂

【分子量】137.56576

【元素组成】C 34.92% H 5.86% Cl 25.77% N 10.18% O 23.26%

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)

Efletirizine can be obtained by two similar ways: 1) The condensation of 1-[bis(4-fluorophenyl)methyl]piperazine (I) with 2-(2-chloroethoxy)acetamide (II) by means of Na2CO3 in hot xylene gives 2-[2-[4-[bis(4-fluorophenyl)methyl]piperazin-1-yl]ethoxy]acetamide (III), which is then hydrolyzed with 4N NaOH in refluxing ethanol. 2) The condensation of 1-[bis(4-fluorophenyl)methyl]piperazine (I) with 2-(2-chloroethoxy)acetic acid methyl ester (IV) by means of Na2CO3 in hot xylene gives 2-[2-[4-[bis(4-fluorophenyl)methyl]piperazin-1-yl]ethoxy]acetic acid methyl ester amide (V), which is then hydrolyzed with 1N KOH in refluxing ethanol.

参考文献中间体

合成目标

【1】 Graul, A.; Leeson, P.; Castañer, R.M.; Efletirizine. Drugs Fut 1997, 22, 6, 626.
【2】 Baltes, E.; De Lannoy, J.; Rodriguez, L. (UCB SA); Novel 2-[4-(diphenylmethyl)-1-piperazinyl]acetic acids and their amides, process for their preparation and pharmaceutical compsns. Containing them. EP 0058146; US 4525358 .

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)	16838	1-Bis(4-fluorophenyl)methyl piperazine; 1-[bis(4-fluorophenyl)methyl]piperazine	27469-60-9	C₁₇H₁₈F₂N₂	详情	详情
(II)	16839	2-(2-chloroethoxy)acetamide		C₄H₈ClNO₂	详情	详情
(III)	16840	2-(2-[4-[bis(4-fluorophenyl)methyl]piperazino]ethoxy)acetamide		C₂₁H₂₅F₂N₃O₂	详情	详情
(IV)	16841	methyl 2-(2-chloroethoxy)acetate		C₅H₉ClO₃	详情	详情
(V)	16842	methyl 2-(2-[4-[bis(4-fluorophenyl)methyl]piperazino]ethoxy)acetate		C₂₂H₂₆F₂N₂O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XI)

In a further procedure, racemic (4-chlorophenyl)phenylmethyl amine (V) was resolved by means of L-tartaric acid. The undesired (S)-enantiomer (VII) could be recovered by racemization to (V) upon treatment with 2-hydroxybenzaldehyde and NaOMe. The required (R)-enantiomer (VI) was condensed with N,N-bis(chloroethyl)-p-toluenesulfonamide (VIII) in refluxing diisopropylethylamine to provide the N-tosyl piperazine (IX). Deprotection of the p-toluenesulfonamide of (IX) was achieved by treatment with HBr in the presence of 4-hydroxybenzoic acid. The resulting piperazine (X) was alkylated with either (2-chloroethoxy)acetamide (XI) or methyl (2-chloroethoxy)acetate (XIII), affording the N-alkylated piperazines (XII) and (XIV), respectively. The title carboxylic acid was then obtained by hydrolysis of amide (XII) with aqueous HCl or, alternatively, by hydrolysis of ester (XIV) with ethanolic KOH.

参考文献中间体

合成目标

【1】 Bodson, G.; Gobert, J.; Cossement, E. (UCB SA); Enantiomers of 1-[4-(chlorophenyl)phenylmethyl]-4-(methylphenyl)sulfonyl piperazine. EP 0617028 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(V)	30407	p-Chloro benzhydryl amine; (4-Chlorophenyl)(phenyl)methylamine; (4-Chlorophenyl)(phenyl)methanamine		C₁₃H₁₂ClN	详情	详情
(VI)	30408	(R)-(4-chlorophenyl)(phenyl)methylamine; (R)-(4-chlorophenyl)(phenyl)methanamine		C₁₃H₁₂ClN	详情	详情
(VII)	30413	(S)-(4-chlorophenyl)(phenyl)methylamine; (S)-(4-chlorophenyl)(phenyl)methanamine		C₁₃H₁₂ClN	详情	详情
(VIII)	30409	N,N-bis(2-chloroethyl)-4-methylbenzenesulfonamide	42137-88-2	C₁₁H₁₅Cl₂NO₂S	详情	详情
(IX)	30410	1-[(R)-(4-chlorophenyl)(phenyl)methyl]-4-[(4-methylphenyl)sulfonyl]piperazine		C₂₄H₂₅ClN₂O₂S	详情	详情
(X)	30404	1-[(R)-(4-chlorophenyl)(phenyl)methyl]piperazine		C₁₇H₁₉ClN₂	详情	详情
(XI)	16839	2-(2-chloroethoxy)acetamide		C₄H₈ClNO₂	详情	详情
(XII)	30411	2-(2-[4-[(R)-(4-chlorophenyl)(phenyl)methyl]-1-piperazinyl]ethoxy)acetamide		C₂₁H₂₆ClN₃O₂	详情	详情
(XIII)	16841	methyl 2-(2-chloroethoxy)acetate		C₅H₉ClO₃	详情	详情
(XIV)	30412	methyl 2-(2-[4-[(R)-(4-chlorophenyl)(phenyl)methyl]-1-piperazinyl]ethoxy)acetate		C₂₂H₂₇ClN₂O₃	详情	详情

Extended Information