ethyl 2-oxo-2-(phenacylamino)acetate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: P2S5 (25.5 g, 114.7 mmol) was added to a solution of ethyl 2-oxo-2-((2-oxo-2-phenylethyl)amino)acetate (13.5 g, 57.39 mmol) in dry CHCl3 (150 mL), and the resulting reaction mixture was heated to reflux for 5 h. The reaction mixture was quenched with water and the organic product was extracted with CHCl3. The combined extracts were washed with H2O and brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 60-120 mesh, eluent 10-15% EtOAc in petroleum ether) to afford ethyl 5-phenylthiazole-2-carboxylate (10 g, yield 75%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 8.16 (s, 1H), 7.64-7.62 (m, 2H), 7.48-7.39 (m, 3H), 4.53-4.47 (q, J=7.0 Hz, 2H), 1.49-1.45 (t, J=7.2 Hz, 3H). MS (ESI) m/z: Calculated for C12H11NO2S: 233.05. found: 234.0 (M+H)+. the resulting reaction mixture was heated to reflux for 5 h The reaction mixture was quenched with water the organic product was extracted with CHCl3 The combined extracts were washed with H2O and brine dried over anhydrous sodium sulfate concentrated under reduced pressure The crude product was purified by column chromatography (silica gel 60-120 mesh, eluent 10-15% EtOAc in petroleum ether)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Triethylamine (36 mL, 262.1 mmol) was added to a solution of 2-aminoacetophenone hydrochloride (15.0 g, 87.39 mmol) in dry CH2Cl2 (300 mL), followed by ethyl chlorooxoacetate (10 mL, 87.39 mmol) at 0° C. The reaction mixture was allowed to warm up to room temperature and stirred for 16 h. The mixture was then diluted with water and extracted with EtOAc. The combined extracts were washed with H2O and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel 60-120 mesh, eluent 20-30% EtOAc in petroleum ether) to afford ethyl 2-oxo-2-((2-oxo-2-phenylethyl)amino)acetate (13.5 g, yield 66%). 1H NMR (400 MHz, CDCl3) δ 8.09 (br s, 1H), 8.02-8.00 (m, 2H), 7.68-7.64 (m, 1H), 7.55-7.51 (m, 2H), 4.85-4.84 (d, J=4.9 Hz, 2H), 4.44-4.39 (q, J=7.0 Hz, 2H), 1.44-1.41 (t, J=7.2 Hz, 3H). MS (ESI) m/z: Calculated for C12H13NO4: 235.08. found: 236.2 (M+H)+. extracted with EtOAc The combined extracts were washed with H2O and brine dried over anhydrous sodium sulfate concentrated under reduced pressure The crude product was purified by column chromatography (silica gel 60-120 mesh, eluent 20-30% EtOAc in petroleum ether)