Sodium ethoxide → 5-Bromo-2-(2,6-difluorophenyl)pyrimidine-4-carboxylic acid

HRID 879142Notes

Reaction equation

HRID 879142 reaction equation
CC[O-].[Na+].Cl.[F:6][C:7]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[C:8]=1[C:9](=[NH:11])[NH2:10].[C:17]([OH:25])(=[O:24])/[C:18](=[C:20](\[CH:22]=O)/[Br:21])/Br>CCO>[Br:21][C:20]1[C:18]([C:17]([OH:25])=[O:24])=[N:11][C:9]([C:8]2[C:7]([F:6])=[CH:15][CH:14]=[CH:13][C:12]=2[F:16])=[N:10][CH:22]=1

Participants

5

Reactant 3

HCID 2723922Sodium ethoxideHCID 3033972Mucobromic AcidHCID 463184242,6-Difluorobenzamidine hydrochloride

Product 1

HCID 666523345-Bromo-2-(2,6-difluorophenyl)pyrimidine-4-carboxylic acid

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent3×

Procedure

A 2.68 M NaOEt in EtOH solution (3 eq) was added to an ice-bath cooled mixture of 2,6-difluorobenzimidamide hydrochloride (2 eq) in EtOH (0.1 M). The resulting mixture was allowed to warm to rt and stirred under N2 for 30 min. To the reaction mixture was added drop wise a solution of mucobromic acid (1 eq) in EtOH and the reaction was heated in a 50° C. oil bath for 2.5 hr. After cooling to rt the reaction mixture was concentrated in vacuo. H2O and 1.0 N NaOH were added and the aqueous mixture was washed with EtOAc. The aqueous phase was acidified to pH=4 with 1.0 N HCl then extracted with EtOAc. Combined organic extracts were washed once with brine, then dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 5-bromo-2-(2,6-difluorophenyl)pyrimidine-4-carboxylic acid. The crude product was used for the next step without further purification. LC/MS (m/z): 316.9 (MH+). LC: Rt: 2.426 min.

Workup

  1. temperaturecooled
  2. temperaturethe reaction was heated in a 50° C. oil bath for 2.5 hr
  3. temperatureAfter cooling to rt the reaction mixture
  4. concentrationwas concentrated in vacuo
  5. additionH2O and 1.0 N NaOH were added
  6. washthe aqueous mixture was washed with EtOAc
  7. extractionthen extracted with EtOAc
  8. washCombined organic extracts were washed once with brine
  9. dry with materialdried over anhydrous Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8f36631002344c52b876c7d6c3f190a6
Source dataset
uspto-grants-2015_03
Patent number
US08987457B2

Reaction notes

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