Phosphorus oxychloride → 2-Isopropyl-thiazole-4-carboxylic acid [6-acetyl-2-chloro-3-(2,2-dimethoxy-ethoxy)-phenyl]-amide

Participants

Reaction Conditions

Reaction Steps

1-[2-amino-3-chloro-4-(2,2-dimethoxy-ethoxy)phenyl]-ethanone (3.98 g, 14.6 mmol) and 2-isopropyl-thiazole-4-carboxylic acid (2.5 g, 14.6 mmol) was dissolved in pyridine (40 mL) and was cooled to −10° C. POCl3 (1.74 mL, 19.0 mmol) was added dropwise. The reaction was stirred at −10° C. for 2 hours. The reaction was quenched with CH3OH (5 mL). After 15 minutes, the reaction was taken up in EtOAc and extracted with 2N HCl(aq). The organic layer was dried with Na2SO4, filtered and was concentrated. 2-Isopropyl-thiazole-4-carboxylic acid [6-acetyl-2-chloro-3-(2,2-dimethoxy-ethoxy)-phenyl]-amide (5.58 g, 89%) was isolated by silica gel chromatography as a white solid.

Provenance & Evidence