Formamidine acetate → 5-Chloropyrimidine-4-carboxylic acid

HRID 1390309Notes

Reaction equation

HRID 1390309 reaction equation
C[O-].[Na+].[C:4]([OH:12])(=[O:11])/[C:5](=[C:7](\[CH:9]=O)/[Cl:8])/Cl.C(O)(=O)C.[CH:17]([NH2:19])=[NH:18]>CO>[C:4]([C:5]1[C:7]([Cl:8])=[CH:9][N:19]=[CH:17][N:18]=1)([OH:12])=[O:11]

Participants

5

Reactant 3

HCID 160693Formamidine acetateHCID 2771871Mucochloric AcidHCID 10942334Sodium Methoxide

Product 1

HCID 200293965-Chloropyrimidine-4-carboxylic acidYield 35.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Sodium methoxide (162 g) is added to a solution of mucochloric acid (169 g) and formamidine acetate (208 g) in methanol (3 liters) over the course of 20 minutes, and the reaction mixture is heated for 1 hour at 35°-40° C., and then for one and a half hours under reflux. The solvent is removed and water (500 cc) is added to the residue. The aqueous mixture is extracted with ethyl acetate (2 liters). The aqueous phase is brought to pH 1 by the addition of concentrated hydrochloric acid, and the aqueous phase is extracted with ethyl acetate (5 liters). The organic phase is dried over anhydrous magnesium sulphate, filtered and then concentrated to dryness. The residue is washed with diethyl ether (300 cc) and then with diisopropyl ether (600 cc). 4-Carboxy-5-chloropyrimidine (55.6 g), melting at 190° C., is obtained.

Workup

  1. temperaturethe reaction mixture is heated for 1 hour at 35°-40° C.
  2. temperaturefor one and a half hours under reflux
  3. customThe solvent is removed
  4. additionwater (500 cc) is added to the residue
  5. extractionThe aqueous mixture is extracted with ethyl acetate (2 liters)
  6. additionThe aqueous phase is brought to pH 1 by the addition of concentrated hydrochloric acid
  7. extractionthe aqueous phase is extracted with ethyl acetate (5 liters)
  8. dry with materialThe organic phase is dried over anhydrous magnesium sulphate
  9. filtrationfiltered
  10. concentrationconcentrated to dryness
  11. washThe residue is washed with diethyl ether (300 cc)

Sources & evidence

ORD record
ord-c455bc81688046a1b3fd7ae7f5ba20ae
Source dataset
uspto-grants-1979_02
Patent number
US04138487

Reaction notes

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