Hydrochloric Acid → Ethyl 3-chloro-2-cyanobenzoate

Participants

Reaction Conditions

Reaction Steps

Hydrochloric acid (4.57 mL, 150 mmol) was added to a suspension of the ethyl 2-amino-3-chlorobenzoate (1.5 g, 7.51 mmol) in water (40 mL) and the mixture was cooled to 0° C. [note: compound did not go into solution] To this cooled mixture was added sodium nitrite (0.518 g, 7.51 mmol) portionwise keeping the temperature below 5° C. After addition the reaction was stirred for 40 mins. A small amount of toluene (3 ml) was added to aid dissolution. The mixture was then basified to pH˜6 by the addition of Na2CO3. In a separate flask potassium cyanide (2.202 g, 33.8 mmol) was added portionwise to a biphasic solution of copper(II) sulfate (1.439 g, 9.02 mmol) in water (15 mL) and toluene (15 mL) at 0° C. [note: exothermic reaction] After addition the now brown mixture was heated to 60° C. To this was added the diazonium salt dropwise via a dropping funnel (mixture kept at 0° C. during addition). After addition the reaction was stirred at 70° C. for 1 hr. The reaction was cooled and EtOAc was added. The organic layer was collected, dried (Na2SO4) and the solvent evaporated to afford a crude dark brown oil. LCMS: 2 major peaks+1 minor peak present. (One major peak corresponds to the SM—no mass ion observed). The crude material was purified by chromatography, SP4, 100 g SNAP, 0 to 100% EtOAc/i-Hexane (fasted eluting first). The desired product was identified in 398 mg.

Provenance & Evidence