[H-].[Na+].[F:3][C:4]([F:16])([F:15])[C:5]1[N:6]=[C:7]([C:10]2[S:11][CH:12]=[CH:13][N:14]=2)[NH:8][CH:9]=1.Br[CH2:18][C:19]([O:21][CH3:22])=[O:20]>C1COCC1.O.[Cl-].[Na+].O>[F:16][C:4]([F:3])([F:15])[C:5]1[N:6]=[C:7]([C:10]2[S:11][CH:12]=[CH:13][N:14]=2)[NH:8][CH:9]=1.[CH3:22][O:21][C:19](=[O:20])[CH2:18][N:8]1[CH:9]=[C:5]([C:4]([F:3])([F:15])[F:16])[N:6]=[C:7]1[C:10]1[S:11][CH:12]=[CH:13][N:14]=1
To a suspension of NaH (109 mg of a 60% dispersion in mineral oil, 2.74 mmol) in THF (10 mL) at 0° C. under N2 is added a solution of 2-(4-trifluoromethyl-1H-imidazol-2-yl)-thiazole (500 mg, 2.28 mmol) in THF (4 mL) via cannula, followed by a 1 mL rinse. The mixture is stirred at 0° C. for 30 min and then treated with methyl bromoacetate (0.28 mL, 2.97 mmol). The reaction mixture is stirred overnight while slowly warming to rt. It is then diluted with H2O (10 mL) and the resulting mixture stirred vigorously for 5 min. The mixture is further diluted with some brine and then extracted twice with EtOAc. The combined extracts are dried over Na2SO4 and concentrated. The crude material is purified by flash chromatography on silica gel. Elution with 4:1 hexanes-EtOAc followed by 3:1 hexanes-EtOAc affords unreacted 2-(4-trifluoromethyl-1H-imidazol-2-yl)-thiazole as well as (2-thiazol-2-yl-4-trifluoromethyl-imidazol-1-yl)-acetic acid methyl ester. 1H NMR (CDCl3, 400 MHz) δ 7.82 (d, J=3.2 Hz, 1H), 7.40 (d, J=3.2 Hz, 1H), 7.35 (s, 1H), 5.41 (s, 2H), 3.77 (s, 3H) ppm.
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