Hydrochloric Acid → HCID 66744051, compound

Participants

Reaction Steps

A mixture of methyl 5-bromo-3-[(trifluoroacetyl)amino]thiophene-2-carboxylate (500 mg, 1.55 mmol), (2-bromoethoxy) (tert-butyl)dimethylsilane (0.99 mL, 4.66 mmol), cesium carbonate (1.52 g, 4.66 mmol), sodium iodide (24 mg, 0.16 mmol) and DMF (3 mL) was microwave-irradiated at 130° C. for 1.5 h. Then, water was added to quench the reaction. The organic materials were extracted with EtOAc. The combined extracts were washed with water and brine, dried over Na2SO4 and filtered. After removal of the solvent at reduced pressure, the residue was dissolved in MeOH (20 mL). To the solution were added potassium carbonate (1.86 g) and water (5 mL). The mixture was stirred at room temperature for 2 h. After removal of the solvent at reduced pressure, the organic materials were extracted with EtOAc. The combined extracts were washed with brine, dried over Na2SO4 and filtered. After removal of the solvent at reduced pressure, the residue was purified by column chromatography (Purif, silica gel, hexane to 80:20 hexane/EtOAc) to give a yellow oil. The oil was mixed with MeOH (4 mL), water (2 mL) and sodium hydroxide (147 mg, 3.68 mmol). The mixture was stirred at 70° C. for 6 h. Then, 6 M aqueous HCl (0.39 mL) was added to the mixture to adjust the pH to 10. After removal of the solvent at reduced pressure, the residue was mixed with ammonium chloride (1.32 g, 24.6 mmol), triethylamine (3.4 mL, 24.6 mmol) and DMF (6.0 mL). After stirring at room temperature for 5 min, 1-hydroxybenzotriazole (997 mg, 7.38 mmol) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (1.41 g, 7.38 mmol) were added. After stirring at room temperature for 18 h, water and EtOAc were added to quench the reaction. The organic materials were extracted with EtOAc. The combined extracts were washed with water and brine, dried over Na2SO4 sulfate and filtered. After removal of the solvent at reduced pressure, the residue was purified by column chromatography (Purif, silica gel, hexane to EtOAc) to give the title compound (108 mg, 26%) as a pale brown solid:

Provenance & Evidence