Tetrahydrofuran → 6,7-Dichloro-2,3-dimethoxyquinoxaline-5-carboxylic Acid

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Reaction Steps

Lithium diisopropylamide mono(tetrahydrofuran) (1.5M in cyclohexane, 15.5 mL, 23.3 mmol) was added to a stirred suspension of 6,7-dichloro-2,3-dimethoxyquinoxaline (Preparation 1, 5.0 g, 19.3 mmol) in dry tetrahydrofuran (150 mL) at −78° C. under nitrogen. The reaction mixture was stirred at this temperature for 1 hour, then anhydrous carbon dioxide was bubbled through the solution at −78° C. for 1 hour. Saturated aqueous ammonium chloride solution (80 mL) was added and the resulting mixture was allowed to reach room temperature, acidified to pH 1 using 2M aqueous hydrochloric acid solution and extracted with ethyl acetate (3×50 mL). The combined organic extracts were then extracted with 1M aqueous sodium hydroxide solution. The aqueous solution was acidified to pH 1 using 2M aqueous hydrochloric acid solution and extracted with dichloromethane (3×50 mL). The combined dichloromethane extracts were dried (MgSO4) and concentrated under reduced pressure to give the title compound (4.0 g, 68%) as a pale brown solid, mp 230-232° C.

Provenance & Evidence