2-(4-(trifluoromethyl)phenyl)thiazole-5-carbaldehyde synthesis

Yield:914348-80-4 88%

Reaction Conditions:

with tetrakis(triphenylphosphine) palladium⁽⁰⁾;sodium carbonate in ethanol;toluene at 85; for 6 h;Inert atmosphere;

Steps:

7.A.1 Step 1: 2-(4-Fluorophenyl)thiazole-5-carbaldehyde

To a solution of 2-bromothiazole-5-carbaldehyde (5.0 g, 26.04 mmol) in toluene (150 mL) and ethanol (75 mL) was added (4-fluorophenyl)boronic acid (7.29 g, 52.08 mmol), 2M sodium carbonate solution (73.58 mL), Pd(PPh₃)₄ (1.5 g, 1.3 mmol) under argon atmosphere. The resulting mixture was heated at 85°C for 6 h. The reaction mixture was concentrated under reduced pressure, the residue was diluted with water (150 mL), and extracted with ethyl acetate (5 x 500 mL). The organic layer was dried over Na₂S0₄, filtered and concentrated under reduced pressures to obtain crude product. The crude product was purified by Combiflash chromatography (Mobile phase: 10% ethyl acetate in hexane) to give 2-(4- fluorophenyl)thiazole-5-carbaldehyde as off-white solid (200 mg, 88% yield). IH NMR (400 MHz, DMSO-d₆): δ 10.06 (s, IH), 8.74 (s, IH), 8.14-8.11 (m, 2H), 7.39 (t, 2H); LC-MS m/z calculated for [M+H]⁺ 208.02, found 207.9

References:

WO2013/49559,2013,A1 Location in patent:Page/Page column 52