Dimethylformamide → 6-Chloro-3-pyridinecarbonitrile

Temperature

25 °C

Oxalyl chloride (40 mL) was added dropwise at 0° C. to a suspension of 6-chloropyridine-3-carboxylic acid (18 g, 114 mmol) in 300 mL of DCM with 3 mL of DMF. The mixture was stirred at 25° C. for 2 hours and the clear solution was concentrated to dryness under reduced pressure. The residue was dissolved in 100 mL of anhydrous acetonitrile and then added to 500 mL of diluted aqueous NH3.H2O at 0° C. The mixture was stirred for 30 minutes then extracted with EtOAc twice. The combined EtOAc layers were washed with water and brine, dried over anhydrous Na2SO4 and concentrated. The residue was dissolved in 100 mL of DMF and cooled to 0° C. with ice/water bath. Cyanuric chloride (21.2 g, 114.9 mmol) was added and the mixture was stirred for 2 hours at 0° C. and then poured into ice/water. The resulting solid was collected by filtration, washed with water, dissolved in DCM, dried over anhydrous Na2SO4 and concentrated to afford 6-Chloropyridine-3-carbonitrile.

1. concentrationthe clear solution was concentrated to dryness under reduced pressure
2. dissolutionThe residue was dissolved in 100 mL of anhydrous acetonitrile
3. additionadded to 500 mL of diluted aqueous NH3.H2O at 0° C
4. stirringThe mixture was stirred for 30 minutes
5. extractionthen extracted with EtOAc twice
6. washThe combined EtOAc layers were washed with water and brine
7. dry with materialdried over anhydrous Na2SO4
8. concentrationconcentrated
9. dissolutionThe residue was dissolved in 100 mL of DMF
10. temperaturecooled to 0° C. with ice/water bath
11. stirringthe mixture was stirred for 2 hours at 0° C.
12. filtrationThe resulting solid was collected by filtration
13. washwashed with water
14. dissolutiondissolved in DCM
15. dry with materialdried over anhydrous Na2SO4
16. concentrationconcentrated

ORD record

ord-9351921b874746608a7b114e65a793be

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08999990B2