Sulfuric Acid → 2,6-Dichloro-5-fluoronicotinamide

HRID 2092857Notes

Reaction equation

HRID 2092857 reaction equation
[Cl:1][C:2]1[N:9]=[C:8]([Cl:10])[C:7]([F:11])=[CH:6][C:3]=1[C:4]#[N:5].S(=O)(=O)(O)[OH:13]>O>[Cl:1][C:2]1[N:9]=[C:8]([Cl:10])[C:7]([F:11])=[CH:6][C:3]=1[C:4]([NH2:5])=[O:13]

Participants

4

Reactant 2

HCID 1118Sulfuric AcidHCID 27338492,6-Dichloro-5-fluoro-3-pyridinecarbonitrile

Product 1

HCID 27740222,6-Dichloro-5-fluoronicotinamideYield 82%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

A 12-L 3-neck round bottom flask equipped with overhead stirrer, refluxing condenser, and N2 inlet/outlet was charged with 2,6-dichloro-5-fluoronicotinonitrile (2.0 kg, 1.0 eq). Concentrated sulfuric acid (4.93 L) was added and the mixture was stirred at RT until most of the brown solids had dissolved. Next, the reaction mixture was stirred at 65° C. for 1 h. The dark-brown solution was cooled to a temperature <10° C. using an ice bath. The reaction mixture was added to a 50-L round bottom flask, which contained de-ionized water (24.7 L) that had been cooled to a temperature <10° C., using a peristaltic pump. The reaction mixture was added to the water quench over a 2.3 h period, which kept the internal temperature of the mixture below 21° C. The resulting slurry was filtered through a Buchner funnel fitted with a Sharkskin filter paper. The 50-L RBF was rinsed with water (3×4 L) and the rinses were used to wash the filter cake. The filter cake was conditioned for 50 min, transferred to a drying tray, and was dried under high vacuum at 40-50° C. for 24 h and then at 20-25° C. for 18 h to give the title compound as a beige solid (896.4 g, 82%). 1H NMR (500 MHz, DMSO-d6) δ ppm 7.94 (s, 1H), 8.10 (s, 1H), 8.24 (d, 1H). [M+H] calc'd for C6H3Cl2FN2O, 209. found, 209.

Workup

  1. customA 12-L 3-neck round bottom flask equipped with overhead stirrer
  2. temperaturerefluxing condenser, and N2 inlet/outlet
  3. dissolutionhad dissolved
  4. stirringNext, the reaction mixture was stirred at 65° C. for 1 h
  5. temperatureThe dark-brown solution was cooled to a temperature <10° C.
  6. additionThe reaction mixture was added to a 50-L round bottom flask
  7. temperaturehad been cooled to a temperature <10° C.
  8. customquench over a 2.3 h period
  9. customthe internal temperature of the mixture below 21° C
  10. filtrationThe resulting slurry was filtered through a Buchner funnel
  11. customfitted with a Sharkskin
  12. filtrationfilter paper
  13. washThe 50-L RBF was rinsed with water (3×4 L)
  14. washto wash the filter cake
  15. customwas dried under high vacuum at 40-50° C. for 24 h

Sources & evidence

ORD record
ord-85bc9a9247934732a6bfddec822e2306
Source dataset
uspto-grants-2013_05
Patent number
US08440689B2

Reaction notes

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