[I:1]N1C(=O)CCC1=O.[F:9][C:10]1[CH:11]=[C:12]([CH:16]=[CH:17][C:18]=1[CH3:19])[C:13]([OH:15])=O.S(Cl)(Cl)=O.C(=O)([O-])[O-].[Na+].[Na+].[CH:30]1([NH2:33])[CH2:32][CH2:31]1>FC(F)(F)S(O)(=O)=O>[CH:30]1([NH:33][C:13](=[O:15])[C:12]2[CH:16]=[C:17]([I:1])[C:18]([CH3:19])=[C:10]([F:9])[CH:11]=2)[CH2:32][CH2:31]1
N-Iodosuccinimide (3.31 g, 20 mmol) was added in portions over 3 hours to a solution of 3-fluoro-4-methylbenzoic acid (2.27 g, 20 mmol) in trifluoromethanesulphonic acid (15 mL) kept at 0° C. Subsequently, the mixture was allowed to warm to room temperature and was stirred overnight. The reaction mixture was poured into ice/water and the precipitate that formed was collected by filtration and washed with water. The solid was dissolved in ethyl acetate, the organic layer was washed with saturated aqueous sodium thiosulphate solution and brine, dried (MgSO4) and the solvent was removed under vacuum. The residue obtained was treated with thionyl chloride (20 mL) and heated at 100° C. for 2.5 hours. Excess thionyl chloride was removed in vacuo and the residue was dissolved in dichloromethane (20 mL). Sodium carbonate (3.70 g, 35 mmol) and cyclopropylamine (1.90 mL, 27 mmol) were added to the solution and the mixture was stirred at room temperature for 72 hours. The mixture was then filtered and the residue was washed with dichloromethane and ethyl acetate. The combined filtrate and washings were concentrated under vacuum and the residue was purified by flash chromatography (10:1 to 5:1 hexanes/ethyl acetate) to give the title compound (2.13 g, 45%) as a white solid.
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