Dimethylformamide → 4,6-Dichloronicotinamide

Temperature

25 °C

4,6-Dichloro-nicotinic acid (10.3 g, 53.4 mmol) was suspended in CH2Cl2 (200 mL). Oxalyl chloride (14 mL, 158 mmol) was added and the reaction was placed in an ice bath. DMF (1.0 mL) was added and the reaction was fitted with an air cooled condenser. The reaction was stirred for 3 h and allowed to warm to 25° C. The volatiles were removed in vacuo and the crude residue was resuspended in THF (200 mL) and cooled to 0° C. To this stirred suspension was added concentrated aqueous ammonia (75 mL) dropwise and the reaction was allowed to stir for 1 h. The volatiles were removed and the crude was redissolved in EtOAc and poured into brine. The aqueous phase was separated and extracted twice with EtOAc. The organic layers were combined, dried (Na2SO4), decanted and concentrated to afford 4,6-dichloro-nicotinamide as a beige solid (7.27 g, 71%).

1. customthe reaction was placed in an ice bath
2. customthe reaction was fitted with an air
3. temperaturecooled condenser
4. customThe volatiles were removed in vacuo
5. temperaturecooled to 0° C
6. additionTo this stirred suspension was added concentrated aqueous ammonia (75 mL) dropwise
7. stirringto stir for 1 h
8. customThe volatiles were removed
9. dissolutionthe crude was redissolved in EtOAc
10. additionpoured into brine
11. customThe aqueous phase was separated
12. extractionextracted twice with EtOAc
13. dry with materialdried (Na2SO4)
14. customdecanted
15. concentrationconcentrated

ORD record

ord-f1fe4da1396f400ca7d82a9702329305

Source dataset

uspto-grants-2008_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07468382B2