Citric Acid → HCID 68546575, compound

Temperature

5 °C

5-Chloro-2-nitrobenzoic acid (25.0 g, 201.6 mmol) was placed in 250 mL dichloromethane and stirred for 5 minutes. After 17.0 mL triethylamine had been added at 25° C., the yellow suspension dissolved gradually. After storing for 10 minutes, the mixture was cooled to 5° C. Isobutyl chloroformate (16.25 mL, 122.8 mmol) was added by drops without dilution within 15 minutes. The reaction mixture was allowed to reach room temperature while stirring and stirring was continued for 1.5 hours. A light yellow precipitate was formed. The mixture was again cooled to 5° C. and 2,6-dimethoxybenzylamine (20.5 g, 122.8 mmol) was added by portions over a period of 20 minutes. For dilution, another 250 mL dichloromethane was added and the mixture was stirred for 15 minutes at 5° C. and then for 65 hours at room temperature. The reaction was monitored by thin layer chromatography, revealing traces of the starting materials. The batch was mixed with 5% citric acid, whereupon a precipitate formed and was filtered out. Product was still detected in the organic phase, so the organic phase was extracted again with 5% citric acid (1×), washed until neutral with sodium bicarbonate solution (1×) and extracted with sodium chloride solution. The organic phase was dried over sodium sulfate and the solvent was removed in vacuo. The solid yellow residue was suspended in diethyl ether/pentane as solvents, then filtered out and washed with diethyl ether. The two crystal products were combined and a pure 5-chloro-N-(2,6-dimethoxybenzyl)-2-nitrobenzamide was isolated. Yield: 31.3 g (89.2 mmol, 73%).

1. dissolutionthe yellow suspension dissolved gradually
2. waitAfter storing for 10 minutes
3. customto reach room temperature
4. stirringwhile stirring
5. stirringstirring
6. waitwas continued for 1.5 hours
7. customA light yellow precipitate was formed
8. temperatureThe mixture was again cooled to 5° C.
9. stirringthe mixture was stirred for 15 minutes at 5° C.
10. waitfor 65 hours at room temperature
11. customformed
12. filtrationwas filtered out
13. extractionwas extracted again with 5% citric acid (1×)
14. washwashed until neutral with sodium bicarbonate solution (1×)
15. extractionextracted with sodium chloride solution
16. dry with materialThe organic phase was dried over sodium sulfate
17. customthe solvent was removed in vacuo
18. filtrationfiltered out
19. washwashed with diethyl ether

ORD record

ord-25c4eb9813644d8c8a9b8dfb8057894b

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08686002B2