Citric Acid → 3,3-difluoro-N-(2-nitrophenyl)cyclobutanecarboxamide

HRID 869512Notes

Reaction equation

HRID 869512 reaction equation
[F:1][C:2]1([F:9])[CH2:5][CH:4]([C:6]([OH:8])=O)[CH2:3]1.C(N1C=CN=C1)(N1C=CN=C1)=O.[N+:22]([C:25]1[CH:31]=[CH:30][CH:29]=[CH:28][C:26]=1[NH2:27])([O-:24])=[O:23].C(N(CC)CC)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C=O)C.C(O)C>[F:9][C:2]1([F:1])[CH2:3][CH:4]([C:6]([NH:27][C:26]2[CH:28]=[CH:29][CH:30]=[CH:31][C:25]=2[N+:22]([O-:24])=[O:23])=[O:8])[CH2:5]1

Participants

8

Reactant 5

HCID 311Citric AcidHCID 69462-NitroanilineHCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 137777893,3-Difluorocyclobutane-1-carboxylic acid

Product 1

HCID 867213413,3-difluoro-N-(2-nitrophenyl)cyclobutanecarboxamideYield 56%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6228DimethylformamideSolvent

Procedure

[step 1] 3,3-Difluorocyclobutanecarboxylic acid (500 mg, 3.67 mmol) was dissolved in DMF (18 mL), 1,1′-carbonyldiimidazole (1.19 g, 7.35 mmol) was added, and the mixture was stirred at room temperature for 1 hr. To the mixture were added 2-nitroaniline (1.02 g, 7.35 mmol) and triethylamine (1.02 mL, 7.35 mmol), and the mixture was stirred at 80° C. for 13 hr. To the mixture were added 5% aqueous citric acid solution and ethanol (5 mL), and the mixture was stirred for 1 hr. The precipitated crystals were collected by suction filtration to give 3,3-difluoro-N-(2-nitrophenyl)cyclobutanecarboxamide (527 mg, 56%).

Workup

  1. stirringthe mixture was stirred at 80° C. for 13 hr
  2. stirringthe mixture was stirred for 1 hr
  3. filtrationThe precipitated crystals were collected by suction filtration

Sources & evidence

ORD record
ord-8ae585d4d8e64f19b0aa5f45ac670d64
Source dataset
uspto-grants-2015_03
Patent number
US08969345B2

Reaction notes

Loading…