Citric Acid → Ethyl[5-(3,5-difluorophenyl)-5-methyl-2,4-dioxo-3-pyridin-2-ylimidazolidin-1-yl]acetate

HRID 1685382Notes

Reaction equation

HRID 1685382 reaction equation
[CH2:1]([O:3][C:4](=[O:22])[CH2:5][N:6]1[C:10]([C:12]2[CH:17]=[C:16]([F:18])[CH:15]=[C:14]([F:19])[CH:13]=2)([CH3:11])[C:9](=[O:20])[NH:8][C:7]1=[O:21])[CH3:2].[NH2:23][C:24]1C=[CH:28][CH:27]=[CH:26][CH:25]=1.BrC1C=CC=CN=1.C([O-])(=O)C.[K+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>N1C=CC=CC=1.[Cu].[Cu]Cl.CCOC(C)=O>[CH2:1]([O:3][C:4](=[O:22])[CH2:5][N:6]1[C:10]([C:12]2[CH:17]=[C:16]([F:18])[CH:15]=[C:14]([F:19])[CH:13]=2)([CH3:11])[C:9](=[O:20])[N:8]([C:28]2[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=2)[C:7]1=[O:21])[CH3:2]

Participants

10

Reactant 5

HCID 311Citric AcidHCID 6115AnilineHCID 79732-BromopyridineHCID 517044Potassium AcetateHCID 91574597Ethyl[5-(3,5-difluorophenyl)-5-methyl-2,4-dioxoimidazolidin-1-yl]acetate

Product 1

HCID 123216751Ethyl[5-(3,5-difluorophenyl)-5-methyl-2,4-dioxo-3-pyridin-2-ylimidazolidin-1-yl]acetate

Reagents, catalysts & solvents 4

HCID 23978CopperCatalystHCID 62652Cuprous chlorideCatalystHCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Procedure

A stirred solution of ethyl[5-(3,5-difluorophenyl)-5-methyl-2,4-dioxoimidazolidin-1-yl]acetate, isomer A (100 mg, 0.320 mmol, described in Intermediate 7), 2-bromopyridine (0.156 mL, 1.60 mmol), copper powder (71.2 mg, 1.12 mmol), copper (I) chloride (6.34 mg, 0.064 mmol), and potassium acetate (94.0 mg, 0.961 mmol) in pyridine (1.8 mL) was heated at 100° C. for 18 h. The cooled reaction mixture was poured onto 10% citric acid (20 mL) and with EtOAc (3×20 mL). The combined organic extracts were dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by silica gel chromatography, eluting with a gradient of hexane:EtOAc—100:0 to 50:50, to provide the title compound. MS: m/z=390 (M+1).

Workup

  1. customThe cooled reaction mixture
  2. dry with materialThe combined organic extracts were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe crude product was purified by silica gel chromatography
  6. washeluting with a gradient of hexane

Sources & evidence

ORD record
ord-cfcf6faedb6b4c98a25f17fd6a0d0008
Source dataset
uspto-grants-2012_04
Patent number
US08148390B2

Reaction notes

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