Ethyl chloroformate → Cisapride (USP/INN)

HRID 324686

反応式

HRID 324686 の反応式
[NH2:1][C:2]1[C:10]([Cl:11])=[CH:9][C:5]([C:6]([OH:8])=O)=[C:4]([O:12][CH3:13])[CH:3]=1.ClC(OCC)=O.[F:20][C:21]1[CH:39]=[CH:38][C:24]([O:25][CH2:26][CH2:27][CH2:28][N:29]2[CH2:34][CH2:33][CH:32]([NH2:35])[CH:31]([O:36][CH3:37])[CH2:30]2)=[CH:23][CH:22]=1>C(N(CC)CC)C>[CH3:13][O:12][C:4]1[CH:3]=[C:2]([NH2:1])[C:10]([Cl:11])=[CH:9][C:5]=1[C:6]([NH:35][CH:32]1[CH:31]([O:36][CH3:37])[CH2:30][N:29]([CH2:28][CH2:27][CH2:26][O:25][C:24]2[CH:38]=[CH:39][C:21]([F:20])=[CH:22][CH:23]=2)[CH2:34][CH2:33]1)=[O:8]

参加物

5

反応物 3

HCID 10928Ethyl chloroformateHCID 816264-Amino-5-chloro-2-methoxybenzoic acidHCID 136778321-(3-(4-Fluorophenoxy)propyl)-3-methoxypiperidin-4-amine

生成物 1

HCID 2769Cisapride (USP/INN)

試薬・触媒・溶媒 1

HCID 8471Triethylamine溶媒

実験手順

To a solution of 4-amino-5-chloro-2-methoxybenzoic acid (20.2 g) in MIK (250 ml) and triethyl amine (15.3 ml) was slowly dropped ethyl chloroformate (9.6 ml). The reaction mixture was stirred for 30 minutes at room temperature. To the formed mixed anhydride was then added intermediate 2 (28.2 g) and the reaction mixture was stirred for 2 hours at room temperature. Subsequently, the reaction mixture was washed with water (80 ml) and a NaOH solution (6.5% w/v, 50 ml). The organic layer was warmed to 65° C. and methanol (50 ml) and water (8.5 ml) were added. The solution was cooled slowly and stirred for 2 days during which crystallisation occurred, yielding cisapride having a cis/trans ratio higher than 99/1.

後処理

  1. washSubsequently, the reaction mixture was washed with water (80 ml)
  2. temperatureThe organic layer was warmed to 65° C.
  3. additionmethanol (50 ml) and water (8.5 ml) were added
  4. temperatureThe solution was cooled slowly
  5. stirringstirred for 2 days during which crystallisation

出典と根拠

ORDレコード
ord-1ad2eecc9a7044a69e41c565dec8c602
出典データセット
uspto-grants-2001_04
特許番号
US06218542B1

関連ノート

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