Acetamide → HCID 58542717, compound

HRID 2277774Notes

Reaction equation

HRID 2277774 reaction equation
[C:1]([NH2:4])(=[O:3])[CH3:2].[Cl:5][C:6]1[CH:7]=[C:8]([F:13])[C:9](F)=[N:10][CH:11]=1.O.C(O)(=O)CC(CC(O)=O)(C(O)=O)O.[Cl-].[Na+]>O.C1COCC1.CN(C=O)C>[C:1]([NH:4][C:9]1[C:8]([F:13])=[CH:7][C:6]([Cl:5])=[CH:11][N:10]=1)(=[O:3])[CH3:2]

Participants

8

Reactant 4

HCID 178AcetamideHCID 5234Sodium ChlorideHCID 222302-Hydroxy-1,2,3-propanetricarboxylic acid hydrate (1:1)HCID 27832485-Chloro-2,3-difluoropyridine

Product 1

HCID 58542717HCID 58542717, compoundYield 74%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

Under a nitrogen atmosphere, DMF (14 mL) and THF (44 mL) were added to acetamide (6.6 g, 112 mmol), and the mixture was warmed to 50° C. A 1.9 M sodium hexamethyldisilazide THF solution (51 mL, 96 mmol) was added dropwise thereto, and the mixture was stirred for 3 hours at the same temperature. 5-Chloro-2,3-difluoropyridine (7.0 g) was then added, THF (1.4 mL) was further added, and the mixture was stirred for 3 hours at the same temperature. The reaction mixture was cooled to 0° C., an aqueous solution of citric acid monohydrate (20 g) and sodium chloride (4.9 g) in water (35 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 (35 mL), and the solvent was distilled off under reduced pressure. A mixed solvent (70 mL) of heptane and tert-butyl methyl ether (15:1) and water (35 mL) were added to the residue, and the mixture was stirred for 10 minutes at room temperature. The mixture was filtered, and the obtained solid was washed twice with water (35 mL). It was further washed with a mixed solvent (70 mL) of heptane and tert-butyl methyl ether (15:1), and dried under reduced pressure to obtain the title compound (6.5 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 (35 mL)
  6. distillationthe solvent was distilled off under reduced pressure
  7. additionA mixed solvent (70 mL) of heptane and tert-butyl methyl ether (15:1) and water (35 mL) were added to the residue
  8. stirringthe mixture was stirred for 10 minutes at room temperature
  9. filtrationThe mixture was filtered
  10. washthe obtained solid was washed twice with water (35 mL)
  11. washIt was further washed with a mixed solvent (70 mL) of heptane and tert-butyl methyl ether (15:1)
  12. customdried under reduced pressure

Sources & evidence

ORD record
ord-dbf937c04faa4bbf807cbe98a0f61228
Source dataset
uspto-grants-2015_09
Patent number
US09133174B2

Reaction notes

Loading…