Potassium Hydroxide → Rebamipide
Reaction equation
[OH-].[K+].[Cl:3][C:4]1[CH:35]=[CH:34][C:7]([C:8]([NH:10][C:11](C(OCC)=O)([CH2:17][C:18]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[NH:21][C:20](=[O:28])[CH:19]=2)[C:12]([O:14]CC)=[O:13])=[O:9])=[CH:6][CH:5]=1>>[Cl:3][C:4]1[CH:5]=[CH:6][C:7]([C:8]([NH:10][CH:11]([CH2:17][C:18]2[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[NH:21][C:20](=[O:28])[CH:19]=2)[C:12]([OH:14])=[O:13])=[O:9])=[CH:34][CH:35]=1Participants
Procedure
100 ml of anhydrous ethyl alcohol and 2.23 g of sodium ethoxide (96%) were added to a 500 ml flask, and the mixture was cooled down to below 5° C. After adding 7.91 g of diethyl 4-chlorobenzamidomalonate, the resulting solution was stirred at below 5° C. for one hour. 5.00 g of 4-bromomethylquinolinon was added to the mixture and the resulting solution was stirred at the room temperature for 16 hours to produce an intermediate, ethyl 2-(4-chlorobenzoylamino)-2-ethoxycarbonyl-3-[2(1H)-quinolinon-4-yl]propionate. After the completion of the reaction, 3.93 g of potassium hydroxide (90%) was added to the above solution, which was then stirred at the room temperature for about 2 hours. Subsequently, the resulting solution was warmed to about 60° C. and stirred for 4 hours to complete the reaction. The concentrated hydrochloric acid were added to the residue for crystallization. The crystal thus obtained was filtered and then subjected to recrystallization with DMF and water to yield 7.17 g (92.04%) of 2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl]propionic acid.
Workup
- additionwas added to the above solution, which
- temperatureSubsequently, the resulting solution was warmed to about 60° C.
- stirringstirred for 4 hours
- customthe reaction
- customThe crystal thus obtained
- filtrationwas filtered
- customsubjected to recrystallization with DMF and water
Sources & evidence
- ORD record
- ord-d312c1fd4d184324a5f72df7cc6d1f00
- Source dataset
- uspto-grants-2004_01
- Patent number
- US06680386B2
Reaction notes
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