Acetic Acid → Benzoic Acid

HRID 1769600Notes

Reaction equation

HRID 1769600 reaction equation
Cl.N[C:3](N)=N.[O-][CH2:7][CH3:8].[Na+].[Na].[C:11]([OH:14])(=[O:13])[CH3:12].[CH2:15](O)[CH3:16]>>[C:11]([OH:14])(=[O:13])[C:12]1[CH:8]=[CH:7][CH:16]=[CH:15][CH:3]=1

Participants

6

Reactant 5

HCID 176Acetic AcidHCID 702Ethanol2×HCID 5742Guanidine HydrochlorideHCID 2723922Sodium ethoxideHCID 5360545Sodium

Product 1

HCID 243Benzoic Acid

Procedure

A solution of 0.6 g of guanidine hydrochloride in 25 ml of absolute ethanol was added to a solution of sodium ethoxide prepared by reacting 0.26 g of sodium metal with 25 ml of absolute ethanol. After 15 minutes, the NaCl precipitate was filtered off, and 1.42 g of 4-[[(2-amino-3-cyano-6 deuteropyrazin-5-yl)methyl]methylamino]benzoic acid was added to the filtrate. The mixture was refluxed for 2 hours and then concentrated to a small volume. The residue was dissolved in 200 ml of water and filtered to yield a clear solution. The solution was acidified to pH 4-5 with glacial acetic acid, and the precipitate formed upon acidification was collected. The precipitate was sequentially washed with H2O, ethanol and ether, and was dried in a desiccator. A yield of 1.6 g of 4-[[4-amino-7-deuteropteridine-6-yl)-methyl]methylamino]benzoic acid was obtained as yellow solid. This compound had a melting point greater than 300° C., and its IR spectrum showed absorptions at 3460-3200, 2940, 1670, 1615, and 1595 cm1, corresponding to NH2, CH, COOH, C=C, and CN signals. The nmr spectrum showed signals at 3.30 (s, Me), 4.90 (s, CH2), 6.80 (d,3'-and 5'-H, J=9Hz), 7.70 (d,2'-and 4'-H, J=9Hz) and 7.35 (b,NH2) ppm. The compound had a retention time of 9.75 min upon HPLC analysis. HPLC analysis was performed using a C18 column. The column was eluted with 27% MeOH in a 0.1 M Tris buffer of pH 6.7 at a flow rate of 1.5 ml/minute. The FAB mass spectrum showed a protonated molecular ion peak at m/z 327. This peak confirmed that the molecular weight of this compound was 326.

Workup

  1. customprepared
  2. filtrationthe NaCl precipitate was filtered off
  3. addition1.42 g of 4-[[(2-amino-3-cyano-6 deuteropyrazin-5-yl)methyl]methylamino]benzoic acid was added to the filtrate
  4. temperatureThe mixture was refluxed for 2 hours
  5. concentrationconcentrated to a small volume
  6. dissolutionThe residue was dissolved in 200 ml of water
  7. filtrationfiltered
  8. customto yield a clear solution
  9. customthe precipitate formed upon acidification
  10. customwas collected
  11. washThe precipitate was sequentially washed with H2O, ethanol and ether
  12. customwas dried in a desiccator

Sources & evidence

ORD record
ord-d8f2030bdc944dbfabfad0b2a9e0e659
Source dataset
uspto-grants-1995_01
Patent number
US05382582

Reaction notes

Loading…