Sodium ethoxide → 5-Bromo-2-cyclopropylpyrimidine-4-carboxylic acid

HRID 1669653Notes

Reaction equation

HRID 1669653 reaction equation
Cl.[CH:2]1([C:5](=[NH:7])[NH2:6])[CH2:4][CH2:3]1.CC[O-].[Na+].[C:12]([OH:20])(=[O:19])/[C:13](=[C:15](\[CH:17]=O)/[Br:16])/[Br:14]>CCO>[Br:14][C:13]1[CH:12]=[N:7][C:5]([CH:2]2[CH2:4][CH2:3]2)=[N:6][CH:15]=1.[Br:16][C:15]1[C:13]([C:12]([OH:20])=[O:19])=[N:7][C:5]([CH:2]2[CH2:4][CH2:3]2)=[N:6][CH:17]=1

Participants

6

Reactant 3

HCID 2723922Sodium ethoxide2×HCID 2781916Cyclopropanecarboximidamide hydrochlorideHCID 3033972Mucobromic Acid

Product 2

HCID 204444135-Bromo-2-cyclopropylpyrimidineHCID 673522455-Bromo-2-cyclopropylpyrimidine-4-carboxylic acidYield 127.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent3×

Conditions

Temperature
56 °C

Procedure

5-Bromo-2-cyclopropylpyrimidine was prepared by the method of Budesinsky, Z., Coll. Czech. Chem. Commun., 1949, 14, 223-235. Cyclopropanecarboximidamide hydrochloride (2.5 g, 20.7 mmol) was dissolved in EtOH (4 mL), freshly prepared 4.1M NaOEt in EtOH (4.8 mL) was added followed by mucobromic acid (2.7 g, 10.3 mmol). The mixture was heated to 56° C. for 30 minutes, more NaOEt in EtOH (4.1M, 3.2 mL) was added and the reaction was stirred at 56° C. for another 15 minutes and then at room temperature overnight. The solvent was evaporated off, aqueous HCl (2M, 10 mL) was added and the brown solid was filtered off. The aqueous layer was extracted three times with dichloromethane. The combined organic layers were dried and concentrated to give a brown oil that together with the solid gave crude intermediate 5-bromo-2-cyclopropylpyrimidine-4-carboxylic acid (1.6 g). The crude intermediate was heated at 140° C. for 8 minutes to give a brown sticky oil that was then partly dissolved in dichloromethane. The solution was decanted from the mixture and concentrated to give the subtitle compound as an oil (673 mg).

Workup

  1. customat room temperature
  2. customovernight
  3. customThe solvent was evaporated off
  4. additionaqueous HCl (2M, 10 mL) was added
  5. filtrationthe brown solid was filtered off
  6. extractionThe aqueous layer was extracted three times with dichloromethane
  7. customThe combined organic layers were dried
  8. concentrationconcentrated
  9. customto give a brown oil that together with the solid

Sources & evidence

ORD record
ord-0c6440e596a04569b7c746e5b978fa7b
Source dataset
uspto-grants-2011_08
Patent number
US07989620B2

Reaction notes

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