Dimethylamine → 2-chloro-N,N-dimethylpyridine-3-carboxamide

Temperature

70 °C

A mixture of 2-chloronicotinic acid (1 kg, 6.35 mmol) and thionyl chloride (575 mL, 7.88 mmol) 30 mL of DMF and 3.2L of toluene was warmed slowly to 70° C. and heated at 70° C. for 30 minutes. The mixture was allowed to cool to approximately 40° C. and then added to a 40% solution of aqueous dimethylamine (3.2L, 25.5 mmol) at 10° C. such that the reaction mixture did not exceed 28° C. An additional 30 minutes was allowed and then the aqueous layer was separated and extracted with toluene (2×1L). Combined organic layers were dried (Na2 SO4), filtered and concentrated under reduced pressure. The residue was dissolved in 2L of ethyl acetate and 4L of hexanes were added slowly to give a precipitate. The mixture was aged for 16 hours and then an additional 1L of hexanes was added. The mixture was cooled in an ice bath for 2 hours and filtered. The filtered residue was washed with 20% ethyl acetate/hexanes (1×1L) and dried under a stream of air to give 2-chloro-N,N-dimethyl-nicotinamide (924.5 g, 5.01 mmol), m.p. 66°-67° C.

1. temperatureheated at 70° C. for 30 minutes
2. temperatureto cool to approximately 40° C.
3. customdid not exceed 28° C
4. customAn additional 30 minutes
5. customthe aqueous layer was separated
6. extractionextracted with toluene (2×1L)
7. customCombined organic layers were dried (Na2 SO4)
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. dissolutionThe residue was dissolved in 2L of ethyl acetate and 4L of hexanes
11. additionwere added slowly
12. customto give a precipitate
13. temperatureThe mixture was cooled in an ice bath for 2 hours
14. filtrationfiltered
15. washThe filtered residue was washed with 20% ethyl acetate/hexanes (1×1L)
16. customdried under a stream of air

ORD record

ord-47c720e410fc4712adfbfbc6bebeb837

Source dataset

uspto-grants-1997_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05688795