Acetamide → HCID 58542717, compound

HRID 2277771Notes

Reaction equation

HRID 2277771 reaction equation
CN(C=O)C.[C:6]([NH2:9])(=[O:8])[CH3:7].[Cl:10][C:11]1[CH:12]=[C:13]([F:18])[C:14](F)=[N:15][CH:16]=1.Cl>C1COCC1>[C:6]([NH:9][C:14]1[C:13]([F:18])=[CH:12][C:11]([Cl:10])=[CH:16][N:15]=1)(=[O:8])[CH3:7]

Participants

6

Reactant 4

HCID 178AcetamideHCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 27832485-Chloro-2,3-difluoropyridine

Product 1

HCID 58542717HCID 58542717, compoundYield 72.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

Under a nitrogen atmosphere, DMF (200 mL) and THF (830 mL) were added to acetamide (94.8 g, 1.61 mol), and the mixture was warmed to 50° C. A 40 wt % sodium hexamethyldisilazide THF solution (629 g, 1.37 mol) was added dropwise thereto, and the mixture was stirred for 2 hours at the same temperature. 5-Chloro-2,3-difluoropyridine (100.0 g, 0.67 mol) was then added, THF (20 mL) was further added, and the mixture was stirred for 3 hours at the same temperature. The reaction mixture was cooled to 0° C., 2.8 M HCl (500 mL) was added, the mixture was warmed to room temperature, and the organic layer was separated. The organic layer was washed with a 20 wt % sodium chloride aqueous solution (500 mL), and the solvent was distilled off under reduced pressure. THF (500 mL) was added to the residue, and the mixture was heated to 70° C. to dissolve the residue. After cooling to room temperature and confirming the precipitation of solids, n-heptane (1500 mL) was added, and the mixture was further cooled to 0° C. and stirred for 3 hours at that temperature. The precipitated crystals were collected by filtration, washed with a mixed solvent of THF (100 mL) and n-heptane (500 mL), and dried under reduced pressure to obtain the title compound (91.2 g).

Workup

  1. stirringthe mixture was stirred for 3 hours at the same temperature
  2. temperatureThe reaction mixture was cooled to 0° C.
  3. temperaturethe mixture was warmed to room temperature
  4. customthe organic layer was separated
  5. washThe organic layer was washed with a 20 wt % sodium chloride aqueous solution (500 mL)
  6. distillationthe solvent was distilled off under reduced pressure
  7. additionTHF (500 mL) was added to the residue
  8. temperaturethe mixture was heated to 70° C.
  9. dissolutionto dissolve the residue
  10. temperatureAfter cooling to room temperature
  11. customthe precipitation of solids, n-heptane (1500 mL)
  12. additionwas added
  13. temperaturethe mixture was further cooled to 0° C.
  14. stirringstirred for 3 hours at that temperature
  15. filtrationThe precipitated crystals were collected by filtration
  16. washwashed with a mixed solvent of THF (100 mL) and n-heptane (500 mL)
  17. customdried under reduced pressure

Sources & evidence

ORD record
ord-cf652cfba5bc4b888b757abcb4cd9c93
Source dataset
uspto-grants-2015_09
Patent number
US09133174B2

Reaction notes

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