Pyridine → N-methoxy-N-methylcyclopentanecarboxamide

HRID 975157Notes

Reaction equation

HRID 975157 reaction equation
C(Cl)(=O)C(Cl)=O.[CH:7]1([C:12]([OH:14])=O)[CH2:11][CH2:10][CH2:9][CH2:8]1.[CH3:15][NH:16][O:17][CH3:18].N1C=CC=CC=1>CN(C)C=O.ClCCl>[CH:7]1([C:12]([N:16]([CH3:15])[O:17][CH3:18])=[O:14])[CH2:11][CH2:10][CH2:9][CH2:8]1

Participants

7

Reactant 4

HCID 1049PyridineHCID 14232N,O-DimethylhydroxylamineHCID 18840Cyclopentanecarboxylic acidHCID 65578Oxalyl chloride

Product 1

HCID 11147854N-methoxy-N-methylcyclopentanecarboxamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

Oxalyl chloride (7.5 ml, 85 mmol) was added dropwise to a stirred solution of cyclopentanecarboxylic acid (4.56 g, 40 mmol) and dimethylformamide (2 drops) in dichloromethane (20 ml) under nitrogen at room temperature. After 2 hours, the reaction mixture was evaporated under reduced pressure and the residual oxalyl chloride removed azeotropically using dichloromethane. The resulting oil was dissolved in dichloromethane (50 ml) and N,O-dimethylhydroxylamine (4.3 g, 44 mmol) added portionwise to the stirred solution. The resulting mixture was cooled using an ice bath, pyridine (7.1 ml, 88 mmol) added, the cooling bath removed and stirring continued for 18 hours. The reaction mixture was then diluted with dichloromethane (50 ml), washed with 5% aqueous citric acid solution (×2) and saturated brine, dried (Na2SO4) and evaporated under reduced pressure. The residue was purified by chromatography on silica gel, eluting with a solvent gradient of methanol:dichloromethane (0:100 to 2:98), to furnish the required amide as an oil. Rf 0.50 (SS 18). Found: C,59.28; H,9.74; N,8.81. C8H15NO2 ; 0.25 H2O requires C,59.41; H,9.66; N,8.66%.

Workup

  1. customthe reaction mixture was evaporated under reduced pressure
  2. customthe residual oxalyl chloride removed azeotropically using dichloromethane
  3. dissolutionThe resulting oil was dissolved in dichloromethane (50 ml)
  4. temperatureThe resulting mixture was cooled
  5. customthe cooling bath removed
  6. waitcontinued for 18 hours
  7. additionThe reaction mixture was then diluted with dichloromethane (50 ml)
  8. washwashed with 5% aqueous citric acid solution (×2) and saturated brine
  9. dry with materialdried (Na2SO4)
  10. customevaporated under reduced pressure
  11. customThe residue was purified by chromatography on silica gel
  12. washeluting with a solvent gradient of methanol:dichloromethane (0:100 to 2:98)

Sources & evidence

ORD record
ord-61795a32f37440b4aa41036fe6f94578
Source dataset
uspto-grants-1997_03
Patent number
US05607960

Reaction notes

Loading…