(E)-2,3-dibromo-4-oxobut-2-enoic acid → 5-Bromo-2-(2-fluorophenyl)pyrimidine-4-carboxylic acid

HRID 1915899Notes

Reaction equation

HRID 1915899 reaction equation
[O-]CC.[Na+].[F:5][C:6]1[CH:14]=[CH:13][CH:12]=[CH:11][C:7]=1[C:8]([NH2:10])=[NH:9].Br/[C:16](=[C:20](/[Br:23])\[CH:21]=O)/[C:17]([OH:19])=[O:18]>C(O)C>[Br:23][C:20]1[C:16]([C:17]([OH:19])=[O:18])=[N:9][C:8]([C:7]2[CH:11]=[CH:12][CH:13]=[CH:14][C:6]=2[F:5])=[N:10][CH:21]=1

Participants

5

Reactant 3

HCID 2723705(E)-2,3-dibromo-4-oxobut-2-enoic acidHCID 2723922Sodium ethoxideHCID 43230592-Fluorobenzamidine

Product 1

HCID 821686735-Bromo-2-(2-fluorophenyl)pyrimidine-4-carboxylic acid

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

Sodium ethoxide (21 mass % in ethanol; 8.69 mL, 23.268 mmol) was added to an ice-bath cooled mixture of 2-fluorobenzamidine (2.71 g, 15.512 mmol) in ethanol (100 mL). The resulting mixture was allowed to warm to room temperature and stirred at rt (room temperature) under nitrogen for 30 min. To the reaction mixture was added a solution of (E)-2,3-dibromo-4-oxo-but-2-enoic acid (2.00 g, 7.7561 mmol) in ethanol (20 ml). The mixture was heated at 50° C. for 3 h. After cooling to RT, the reaction was concentrated in vacuo. Water and 1M NaOH (˜50 ml) were added and the aqueous mixture was extracted with EtOAc. The aqueous phase was acidified to pH4 with 1N HCl (about 30 ml), then extracted with EtOAc 3×. Combined organic extracts were dried over sodium sulfate, filtered and concentrated to gave 5-bromo-2-(2-fluorophenyl)pyrimidine-4-carboxylic acid, 770 mg.

Workup

  1. temperaturecooled
  2. temperatureThe mixture was heated at 50° C. for 3 h
  3. temperatureAfter cooling to RT
  4. concentrationthe reaction was concentrated in vacuo
  5. additionWater and 1M NaOH (˜50 ml) were added
  6. extractionthe aqueous mixture was extracted with EtOAc
  7. extractionextracted with EtOAc 3×
  8. dry with materialCombined organic extracts were dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-f66b542cb56249499a1599913708a013
Source dataset
uspto-grants-2013_12
Patent number
US08614206B2

Reaction notes

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