Sodium Hydroxide → 4-(2-Fluoro-5-hydroxy-4-methylanilino)-7-hydroxyquinazoline

HRID 634727Notes

Reaction equation

HRID 634727 reaction equation
[OH-].[Na+].Cl.[F:4][C:5]1[CH:22]=[C:21]([CH3:23])[C:20]([O:24]C(OC)=O)=[CH:19][C:6]=1[NH:7][C:8]1[C:17]2[C:12](=[CH:13][C:14]([OH:18])=[CH:15][CH:16]=2)[N:11]=[CH:10][N:9]=1>CO>[F:4][C:5]1[CH:22]=[C:21]([CH3:23])[C:20]([OH:24])=[CH:19][C:6]=1[NH:7][C:8]1[C:17]2[C:12](=[CH:13][C:14]([OH:18])=[CH:15][CH:16]=2)[N:11]=[CH:10][N:9]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 1356711774-(2-Fluoro-5-methoxycarbonyloxy-4-methylanilino)-7-hydroxyquinazoline hydrochloride

Product 1

HCID 1355493894-(2-Fluoro-5-hydroxy-4-methylanilino)-7-hydroxyquinazolineYield 49.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

1M Aqueous sodium hydroxide solution (2.1 ml, 2.1 mmol) was added to a solution of 4-(2-fluoro-5-methoxycarbonyloxy-4-methylanilino)-7-hydroxyquinazoline hydrochloride (400 mg, 1.05 mmol), in methanol (10 ml) and the mixture stirred for 50 minutes at ambient temperature. The solvent was removed by evaporation, the residue dissolved in water and adjusted to pH7 with hydrochloric acid. The aqueous mixture was extracted with ethyl acetate, the extracts washed with brine, dried (MgSO4) and the solvent removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol 95/5 and 80/20. The purified solid was dissolved in methanol and saturated methanolic hydrogen chloride was added. The volatiles were removed by evaporation, the residue was triturated with pentane to give 4-(2-fluoro-5-hydroxy-4-methylanilino)-7-hydroxyquinazoline (149 mg, 44%) as a yellow solid.

Workup

  1. customThe solvent was removed by evaporation
  2. dissolutionthe residue dissolved in water
  3. extractionThe aqueous mixture was extracted with ethyl acetate
  4. washthe extracts washed with brine
  5. dry with materialdried (MgSO4)
  6. customthe solvent removed by evaporation
  7. customThe residue was purified by column chromatography
  8. washeluting with methylene chloride/methanol 95/5 and 80/20
  9. dissolutionThe purified solid was dissolved in methanol
  10. additionsaturated methanolic hydrogen chloride was added
  11. customThe volatiles were removed by evaporation
  12. customthe residue was triturated with pentane

Sources & evidence

ORD record
ord-bddad8ce70344b9681f769619e186ddd
Source dataset
uspto-grants-2001_02
Patent number
US06184225B2

Reaction notes

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