Reaction equation
[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]Participants
5
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
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.
Workup
- washSubsequently, the reaction mixture was washed with water (80 ml)
- temperatureThe organic layer was warmed to 65° C.
- additionmethanol (50 ml) and water (8.5 ml) were added
- temperatureThe solution was cooled slowly
- stirringstirred for 2 days during which crystallisation
Sources & evidence
- ORD record
- ord-1ad2eecc9a7044a69e41c565dec8c602
- Source dataset
- uspto-grants-2001_04
- Patent number
- US06218542B1
Linked notes
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