Triethylamine → 2-Chloro-N-methylnicotinamide

Temperature

95 °C

To a mixture of 63.0 g (0.40 mol) 6-chloronicotinic acid and 37.7 ml (0.52 mol) thionylchloride was added 340 ml toluene and 0.92 ml (12.0 mmol) DMF. The brown suspension was heated to 95° C. and stirred at 95° C. for 1.5 h. The solvent was subsequently removed and the residue treated with 340 ml CH2Cl2. This solution was cooled to 2° C. and treated with 81.0 g (1.2 mol) methylaminhydrochloride. To the so formed brown suspension was added at −2° C. to −6° C. dropwise over 75 min. 167.5 ml (1.2 mol) NEt3 (the reaction was finished after further 30 min.). The reaction mixture was poured onto 400 ml brine and 100 ml sat. aqueous sodium carbonate and extracted. The aqueous phase was extracted with total 2.4 l CH2Cl2. The organic phases were washed with 400 ml sat. aqueous sodium carbonate and 400 ml brine, combined, dried over MgSO4. The solvent was removed under reduced pressure to give 67.5 g (98.9%) product as brown crystals, m.p. 147.5-148.0° C.

1. customThe solvent was subsequently removed
2. additionthe residue treated with 340 ml CH2Cl2
3. temperatureThis solution was cooled to 2° C.
4. additionTo the so formed brown suspension was added at −2° C. to −6° C. dropwise over 75 min
5. extractionextracted
6. extractionThe aqueous phase was extracted with total 2.4 l CH2Cl2
7. washThe organic phases were washed with 400 ml sat. aqueous sodium carbonate and 400 ml brine
8. dry with materialdried over MgSO4
9. customThe solvent was removed under reduced pressure

ORD record

ord-b11b6a41b2564af98a53ee6379206571

Source dataset

uspto-grants-2001_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06297375B1