反应详情

温度

75 °C

Charge a mixture of 7.50 kg (26.66 mol) of 3-amino-1H-indole-2-carboxylic acid ethyl ester, 37.5L of ethanol and 37.5 L of 4M KOH to a 30-gal reactor and heat to 75° C. over 30 min. Monitor the progress of the reaction by HPLC (Column—150×3.9 mm Waters Symmetry C18, 5 micron; mobile phase—20% acetonitrile/80% 0.1% TFA in water; flow rate—1.0 mL/min; wavelength—225 nm; RT: 3-amino-1H-indole-2-carboxylic acid potassium salt—3.3 min; 3-amino-1H-indole-2-carboxylic acid ethyl ester—6.0 min). Typically achieve, a 100% conversion within 3 h. Cool the mixture to 25° C. over 2 h and concentrate at 50–60° C./50 torr to a residue. Add a total of 37.5 L of water and heat the mixture to and hold at 85° C. for 30 min. Cool the mixture to 10° C. over 2 hours, and then further cool to and hold at 5° C. for 2 hours. Filter off the solid that forms, wash with a total of 10 L of 4M KOH solution and air dry. Further dry the solid at 35° C. in a forced air oven for 72 h to give 10.9 kg, 140% yield of the title compound: HPLC analysis 70.7% pure.

1. additionCharge
2. temperatureCool the mixture to 25° C. over 2 h
3. concentrationconcentrate at 50–60° C./50 torr to a residue
4. additionAdd a total of 37.5 L of water
5. temperatureheat the mixture to and
6. waithold at 85° C. for 30 min
7. temperatureCool the mixture to 10° C. over 2 hours
8. temperaturefurther cool to and
9. waithold at 5° C. for 2 hours
10. filtrationFilter off the solid that forms
11. washwash with a total of 10 L of 4M KOH solution and air
12. customdry
13. customFurther dry the solid at 35° C. in a forced air oven for 72 h