[F:1][C:2]([F:9])([F:8])[C:3]1[N:4]=[CH:5][NH:6][CH:7]=1.[H-].[Na+].Br[CH2:13][C:14]([O:16][CH3:17])=[O:15]>C1COCC1>[F:1][C:2]([F:9])([F:8])[C:3]1[N:4]=[CH:5][N:6]([CH2:13][C:14]([O:16][CH3:17])=[O:15])[CH:7]=1To a solution of 4-(trifluoromethyl)-1H-imidazole (10.0 g, 73.5 mmol) in THF (75 mL) at 0° C. was added sodium hydride (60% in mineral oil, 3.25 g, 80.8 mmol) under nitrogen. The mixture was stirred at 0° C. for 30 min. Methyl bromoacetate (1.67 mL, 17.6 mmol) was added and the reaction was stirred for 3 h at room temperature. LC-MS showed the reaction was complete. The solvent was removed under reduced pressure. The crude material was redissolved in diethyl ether and washed with sat. aq. ammonium chloride and 1N HCl aqueous solution. The combined aqueous layer was reextracted with ethyl acetate three times. The combined organic layer was dried over MgSO4, filtered, and evaporated to a mixture of solid and oil. The crude was filtered to remove most of the oil, and the solid was washed with heptane. This yellow solid was triturated in a minimum amount of diethyl ether to wash off the yellow impurities. The material was filtered and the solid was retriturated with diethyl ether again. The filtrate was concentrated and the previous trituration steps were repeated. This afforded (I-36a) as a white solid (9.33 g, 61%); 1H NMR (400 MHz, CDCl3): δ 7.53 (1 H), 7.30 (1 H), 4.73 (2 H), 3.81 (3 H); m/z 209.0 (M+H)+.
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