2,4-Dimethoxybenzylamine → 2-(4-Chloro-phenyl)-4-(2-hydroxy-ethyl)-thiazole-5-carboxylic acid 2,4-dimethoxy-benzylamide

Participants

Reaction Conditions

Reaction Steps

Dissolve 2,4-dimethoxybenzylamine (22.4 g, 134.0 mmol) in CH2Cl2 (300 mL) and cool to 0° C. To the above solution, slowly add a solution of trimethylaluminum (110 mL, 220 mmol; 2 M in toluene) over 35 min while keeping the temperature below 10° C. Stir the resulting solution at room temperature for 45 min and then re-cool to 0° C. Add 2-(4-chloro-phenyl)-6,7-dihydro-pyrano[4,3-d]thiazol-4-one (52.2 g, 120.6 mmol), then allow the resulting slurry to warm to room temperature and stir overnight. Cool the reaction and carefully quench with saturated Rochelle's salt solution (300 mL) over 30 min. Add CH2Cl2 (750 mL), water (400 mL) and diatomaceous earth (100 g) and stir the mixture at room temperature for 30 min, then filter. Collect the solids and triturate with CH2Cl2 (1 L) at 35° C. for 3 h, then filter. Concentrate the filtrate to obtain the title compound (32.2 g). Repeat the trituration step with the second solid cake and obtain an additional 20 g of title compound (90% total yield). 1H NMR (400 MHz, DMSO-d6) δ9.01 (br s, 1H), 7.96 (d, 2H, J=8.5), 7.57 (d, 2H, J=8.5), 7.15 (d, 1H, J=7.9), 6.57 (d, 1H, J=2.6), 6.48 (dd, 1H, J=2.6, 8.5), 5.34 (t, 1H, J=4.3), 4.34 (d, 2H, J=6.6), 3.81 (s, 3H), 3.79 (m, 2H), 3.75 (s, 3H), 3.11 (t, 3H, J=6.6).

Provenance & Evidence