Acetyl chloride → 5-Cyano-2-hydroxybenzamide

Acetyl chloride (43.3 g) was added dropwise with ice-cooling to a solution of 5-cyano-salicylic acid (29.0 g) and triethylamine (54.0 g) in dichloromethane (300 ml). After the addition was complete, the reaction mixture was stirred for 2 hours at ice-cooling temperature to room temperature. The solvent was distilled off under reduced pressure and the residue was extracted by addition of ethyl acetate and an aqueous potassium bisulfate solution. The ethyl acetate layer was washed with saturated saline solution, dried over anhydrous magnesium sulfate. The solvent was distilled off to obtain oil. This oil was dissolved in 1,2-dichloroethane (100 ml), and thionyl chloride (42.4 g) and dimethylformamide (0.5 ml) were added to the mixture, and the resulting mixture was heated under reflux for 1 hour. After air cooling, the solvent was distilled off under reduced pressure, and the residue was dissolved in tetrahydrofuran (100 ml). This solution was added with ice cooling to a mixed solution of aqueous ammonia (100 ml) and tetrahydrofuran (100 ml), and the mixture was stirred for 1 hour. An aqueous potassium bisulfate solution was added to the mixture to adjust to pH 2 to 3, and the mixture was extracted with ethyl acetate-tetrahydrofuran three times. The organic layers were combined and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain crude 5-cyano-salicylamide.

1. additionAfter the addition
2. distillationThe solvent was distilled off under reduced pressure
3. extractionthe residue was extracted by addition of ethyl acetate
4. washThe ethyl acetate layer was washed with saturated saline solution
5. dry with materialdried over anhydrous magnesium sulfate
6. distillationThe solvent was distilled off
7. customto obtain oil
8. temperaturethe resulting mixture was heated
9. temperatureunder reflux for 1 hour
10. temperatureAfter air cooling
11. distillationthe solvent was distilled off under reduced pressure
12. dissolutionthe residue was dissolved in tetrahydrofuran (100 ml)
13. additionThis solution was added with ice cooling to a mixed solution of aqueous ammonia (100 ml) and tetrahydrofuran (100 ml)
14. stirringthe mixture was stirred for 1 hour
15. additionAn aqueous potassium bisulfate solution was added to the mixture
16. extractionthe mixture was extracted with ethyl acetate-tetrahydrofuran three times
17. dry with materialdried over anhydrous magnesium sulfate
18. distillationThe solvent was distilled off under reduced pressure

ORD record

ord-0fc97d898bd54d53b649929318cda5ed

Source dataset

uspto-grants-1993_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05270308