Chloride → 2-(4-Chloro-phenyl)-4-(2-methoxy-ethyl)-thiazole-5-carboxylic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

Add a 1.0 M solution of sufuryl chloride in dichloromethane (20.0 mL, 20.0 mmol) dropwise to a solution of 5-methoxy-3-oxo-pentanoic acid methyl ester (3.0 g, 18.8 mmol) in dichloromethane (20.0 mL) at 0° C. and stir under nitrogen at 0° C. for 2 h. Concentrate the reaction mixture on a rotavap (rotary evaporator), keeping the bath temperature at RT. Add 4-chlorothiobenz-amide (3.67 g, 21.5 mmol) to the residue, followed by methanol (30.0 mL) and heat to 60° C. for 18 h. Quench the reaction with water and extract with EtOAc (2×). Combine the organic portions, wash with brine, dry over MgSO4, filter, and concentrate under vacuum. Purify by flash chromatography on silica gel, using a gradient of EtOAc/Hexane (0-60%) to give the title compound (3.3 g, 57%). Exact mass=311.0, MS (ES+) 312.0 (M+1). 1H NMR (CDCl3): δ 7.89 (d, 2H, J=8.8 Hz), 7.40 (d, 2H, J=8.8 Hz), 3.88 (s, 3H), 3.82 (t, 2H, J=6.8 Hz), 3.47 (t, 2H, J=6.8 Hz), 3.38 (s, 3H).

Provenance & Evidence