Norchlorcyclizine → Cetirizine ethyl ester

HRID 1871007ノート

反応式

HRID 1871007 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[N:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)=[CH:4][CH:3]=1.Cl[CH2:22][CH2:23][O:24][CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27]>C(N(CC)CC)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[N:9]2[CH2:10][CH2:11][N:12]([CH2:22][CH2:23][O:24][CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:13][CH2:14]2)=[CH:6][CH:7]=1

参加物

4

反応物 2

HCID 9340NorchlorcyclizineHCID 10964894Ethyl 2-(2-chloroethoxy)acetate

生成物 1

HCID 9844843Cetirizine ethyl ester収率 89%

試薬・触媒・溶媒 1

HCID 8471Triethylamine溶媒

実験手順

The present inventors have found that when the reaction is performed in a tertiary amine as both solvent and acid scavenger at elevated temperature, significantly higher yield is obtained. Namely, when 1-[(4-chlorophenyl)phenylmethyl]piperazine is reacted in a pressure vessel with ethyl 2-chloroethoxyacetate in triethylamine at 135° C. for 10 hours, ethyl [2-[4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy]acetate is obtained in 89% yield. When catalytic amounts of potassium iodide or tetrabutylammonium iodide are present in the reaction, slightly higher yield is obtained. If triisopropylamine or pyridine are used instead of triethylamine and the reaction is carried out at the same temperature at atmospheric pressure, a drop of 30-40% in the reaction yield is observed.

後処理

  1. customacid scavenger at elevated temperature, significantly higher yield
  2. customis obtained

出典と根拠

ORDレコード
ord-edd692d347b74356a96619ef7662d27f
出典データセット
uspto-grants-2000_08
特許番号
US06100400

反応ノート

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