Ammonium formate → Diethyl (4-amino-2,5-difluorophenyl)propanedioate

HRID 1879110Notes

Reaction equation

HRID 1879110 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[C:5]([F:11])=[CH:4][C:3]=1[CH:12]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[C:13]([O:15][CH2:16][CH3:17])=[O:14].C([O-])=O.[NH4+]>C(O)C.[Pd]>[NH2:8][C:6]1[C:5]([F:11])=[CH:4][C:3]([CH:12]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[C:13]([O:15][CH2:16][CH3:17])=[O:14])=[C:2]([F:1])[CH:7]=1

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 59163358Diethyl (2,5-difluoro-4-nitrophenyl)propanedioate

Product 1

HCID 59163383Diethyl (4-amino-2,5-difluorophenyl)propanedioateYield 99.9%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

10% Pd/C (wet paste, 484 mg) was added to a solution of diethyl (2,5-difluoro-4-nitrophenyl)propanedioate (4.84 g, 15.3 mmol) and ammonium formate (5 eq, 4.81 g, 76.34 mmol) in ethanol (100 mL). The reaction mixture was heated to reflux under argon for one hour. The reaction was allowed to cool and then filtered through celite to remove the Pd residues. The filtrate was evaporated to dryness and then partitioned between ethyl acetate (100 mL) and water (100 mL). The organic layer was separated, dried over magnesium sulfate, filtered and then evaporated to dryness to give the title compound as an orange oil (4.39 g) LC/MS Rt=1.07 min, [MH]+ 288.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux under argon for one hour
  3. temperatureto cool
  4. filtrationfiltered through celite
  5. customto remove the Pd residues
  6. customThe filtrate was evaporated to dryness
  7. custompartitioned between ethyl acetate (100 mL) and water (100 mL)
  8. customThe organic layer was separated
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. customevaporated to dryness

Sources & evidence

ORD record
ord-e8458a7ae14643eea5fc6c13a51fc5e3
Source dataset
uspto-grants-2012_11
Patent number
US08314147B2

Reaction notes

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