[Br:1][C:2]1[C:10]([O:11][CH:12]([F:14])[F:13])=[C:9]([Br:15])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.S(Cl)(Cl)=O.CN(C)C=O.CN[C:27]([NH:34][CH3:35])=[CH:28][C:29]([O:31][CH2:32][CH3:33])=[O:30].[C:36]1(C)C=CC=C[CH:37]=1>O.C(N(CC)CC)C>[CH:35]1([NH:34][CH:27]=[C:28]([C:4](=[O:6])[C:3]2[CH:7]=[CH:8][C:9]([Br:15])=[C:10]([O:11][CH:12]([F:14])[F:13])[C:2]=2[Br:1])[C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH2:37][CH2:36]1
To a mixture of 2.4-dibromo-3-(difluoromethoxy) benzoic acid (10 g) and thionyl chloride (4.38 gm) was added a mixture of toluene (15 ml) and N,N-dimethyl formamide (0.2 ml). The reaction mixture was heated slowly to reflux and stirred at reflux for about 2.5 hours. The reaction mixture was then cooled to 35° C. and added a solution of ethyl 3,3-dimethylaminoacrylate (4.13 gm), and triethylamine (3.79 gm) in toluene (20 ml) drop-wise during a period of about 1 hour maintaining a temperature of 35-40° C. After the addition was over, the reaction temperature was slowly increased to 60-65° C. and stirred the reaction mixture for about 24 hours. Cooled the reaction mixture to 30° C., added water (20 ml) and stirred for about 10 minutes. The organic layer was separated, cooled to about 5° C. and cyclopropylamine (1.82 gm) was added to it drop-wise maintaining temperature at 8-10° C. during a period of about 10 minutes. Stirred the reaction mixture for about 2 hours, solvent was removed under vacuum (˜80% of the original amount) and cooled the reaction mixture to about 20° C. The solid separated was filtered and dried to afford ethyl 3-cyclopropylamino-2-[2,4-dibromo-3(difluoromethoxy) benzoyl]-2-propenoate (10 gm).
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