反应详情

温度

0 °C

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.

1. customthe temperature below 5° C
2. additionAfter addition the reaction
3. custom[note: exothermic reaction]
4. additionAfter addition the now brown mixture
5. temperaturewas heated to 60° C
6. addition(mixture kept at 0° C. during addition)
7. additionAfter addition the reaction
8. stirringwas stirred at 70° C. for 1 hr
9. temperatureThe reaction was cooled
10. customThe organic layer was collected
11. dry with materialdried (Na2SO4)
12. customthe solvent evaporated
13. customto afford a crude dark brown oil
14. customThe crude material was purified by chromatography, SP4, 100 g SNAP, 0 to 100% EtOAc/i-Hexane (fasted eluting first)