Acetamide → HCID 58542717, compound

HRID 2277775Notes

Reaction equation

HRID 2277775 reaction equation
[C:1]([NH2:4])(=[O:3])[CH3:2].CC(C)([O-])C.[K+].[Cl:11][C:12]1[CH:13]=[C:14]([F:19])[C:15](F)=[N:16][CH:17]=1.[Cl-].[NH4+]>CN(C=O)C.C(OCC)(=O)C.O>[C:1]([NH:4][C:15]1[C:14]([F:19])=[CH:13][C:12]([Cl:11])=[CH:17][N:16]=1)(=[O:3])[CH3:2]

Participants

8

Reactant 4

HCID 178AcetamideHCID 25517Ammonium ChlorideHCID 27832485-Chloro-2,3-difluoropyridineHCID 23665647Potassium tert-butoxide

Product 1

HCID 58542717HCID 58542717, compoundYield 56.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

Under a nitrogen atmosphere, a suspension of acetamide (620 mg, 10.5 mmol) and potassium t-butoxide (1.01 g, 10.5 mmol) in DMF (4.5 mL) was heated to 50° C. and stirred for 1.5 hours. It was cooled to 0° C., 5-chloro-2,3-difluoropyridine (450 mg, 3.0 mmol) was added dropwise, DMF (0.45 mL) was further added, and the mixture was stirred at that temperature for 2.5 hours. A saturated ammonium chloride aqueous solution (4.5 mL) and water (4.5 mL) were added to the reaction mixture in that order, and extraction was performed with ethyl acetate (9.0 mL). The aqueous layer was extracted twice with ethyl acetate (9.0 mL), and the combined organic layers were washed with a sodium chloride aqueous solution (4.5 mL) and dried over anhydrous sodium sulfate. A portion (22.1%) of the organic layer was sampled for 1H-NMR quantification, and the solvent was distilled off from the remaining organic layer under reduced pressure. A mixed solvent (7.0 mL) of heptane and t-butyl methyl ether (15:1) was added to the residue to form a suspension, and the suspension was stirred. The precipitated solid was collected by filtration, washed with a mixed solvent (3.5 mL) of heptane and t-butyl methyl ether (15:1), and dried under reduced pressure to obtain the title compound (321 mg, 1.7 mmol).

Workup

  1. temperatureIt was cooled to 0° C.
  2. stirringthe mixture was stirred at that temperature for 2.5 hours
  3. extractionThe aqueous layer was extracted twice with ethyl acetate (9.0 mL)
  4. washthe combined organic layers were washed with a sodium chloride aqueous solution (4.5 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. aliquotA portion (22.1%) of the organic layer was sampled for 1H-NMR quantification
  7. distillationthe solvent was distilled off from the remaining organic layer under reduced pressure
  8. additionA mixed solvent (7.0 mL) of heptane and t-butyl methyl ether (15:1) was added to the residue
  9. customto form a suspension
  10. stirringthe suspension was stirred
  11. filtrationThe precipitated solid was collected by filtration
  12. washwashed with a mixed solvent (3.5 mL) of heptane and t-butyl methyl ether (15:1)
  13. customdried under reduced pressure

Sources & evidence

ORD record
ord-0d23c3ec1c3e49fd8361277f507db0f5
Source dataset
uspto-grants-2015_09
Patent number
US09133174B2

Reaction notes

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