2-[5-(2-CHLOROACETYL)-2-THIENYL]ACETIC ACID synthesis

Yield:851340-07-3 84%

Reaction Conditions:

with hydrogenchloride in water at 20; for 4 h;Heating / reflux;

Steps:

1.1

Example 1 Preparation of N-Hvdroxy-2-r5-(2-phenvlacetylamino-thiazol-4-vl)-thioDhen-2-yl1- acetamide Step 1 Synthesis of [5- (2-Chloro-acetyl)-thiophene-2-yl]-acetic acid methyl ester 0 0 g HCI/MeOH S Me00C CI HOOC CI reflux, 4 hrs To a solution of 463mg [5-(2-Chioro-acetyl)-thiophene-2-yl]-acetic acid in 4 mL MeOH was added 1 mL 37% HCI at room temperature. The reaction was heated to reflux for 4 hours. The reaction was cooled to room temperature, neutralized by saturated aqueous sodium bicarbonate and extracted by dichloromethane. The combined organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel to afford the desired product 411mg (84%). Rf 0. 6 (hexane: ethyl acetate = 1: 1); 1H NMR (CDCI3) : 5 7.67 (d, J= 3.9 Hz, 1H), 7.03 (d, J = 3.9 Hz, 1H), 4.55 (s, 2H), 3.89 (s, 2H), 3.76 (s, 3H); 13C NMR (CDCl3): No. 184.1, 169.7, 145.8, 140.3, 133.3, 128.5, 52.7, 45.4, 35.9; ESIMS (m/z0 233 (M+1)

References:

WO2005/40161,2005,A1 Location in patent:Page/Page column 60