Ethyl chloroformate → Cisapride (USP/INN)

HRID 324686

반응식

HRID 324686 반응식
[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]

참가 물질

5

반응물 3

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

생성물 1

HCID 2769Cisapride (USP/INN)

시약·촉매·용매 1

HCID 8471Triethylamine용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-1ad2eecc9a7044a69e41c565dec8c602
출처 데이터셋
uspto-grants-2001_04
특허 번호
US06218542B1

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