Hydrochloric Acid → 2-(2-fluoro-6-methoxyphenyl)-7-methylquinazolin-4(3H)-one

HRID 2062171Notes

Reaction equation

HRID 2062171 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH3:9])=[CH:5][C:4]=1[NH:10][C:11](=O)[C:12]1[C:17]([O:18][CH3:19])=[CH:16][CH:15]=[CH:14][C:13]=1[F:20])#[N:2].[OH-:22].[Na+].OO.Cl>C(O)C>[F:20][C:13]1[CH:14]=[CH:15][CH:16]=[C:17]([O:18][CH3:19])[C:12]=1[C:11]1[NH:2][C:1](=[O:22])[C:3]2[C:4](=[CH:5][C:6]([CH3:9])=[CH:7][CH:8]=2)[N:10]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 784Hydrogen Peroxide4×HCID 14798Sodium Hydroxide3×HCID 58683864N-(2-cyano-5-methylphenyl)-2-fluoro-6-methoxybenzamide

Product 1

HCID 1361215392-(2-fluoro-6-methoxyphenyl)-7-methylquinazolin-4(3H)-oneYield 89%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a suspension of N-(2-cyano-5-methylphenyl)-2-fluoro-6-methoxybenzamide (31.5 g, 111 mmol) in ethanol (626 mL) was added 6 M aqueous NaOH solution (205 mL). After 10 minutes, 30% aqueous H2O2 (60 mL) was added, forming a slurry. The reaction was heated to reflux for 18 h and cooled to room temperature. NaOH (22.2 g, 0.56 mol) and 30% aqueous H2O2 (26 mL) were added, and the reaction was heated to reflux for six hours. The reaction cooled to room temperature, 30% aqueous H2O2 (45 mL) was added, and the reaction was heated to reflux for 18 h. The reaction was cooled to room temperature, NaOH (10 g, 0.25 mol) and 30% aqueous H2O2 (70 mL) were added, and the reaction was heated to reflux for six hours. The reaction was cooled to room temperature and poured over ice (800 mL). The pH was adjusted to 3-4 by addition of conc. HCl solution, and the precipitated off-white solid was filtered and washed with water (3×40 mL). The solid was dried under vacuum to provide 2-(2-fluoro-6-methoxy-phenyl)-7-methyl-3H-quinazolin-4-one (28 g, 89%).

Workup

  1. customforming a slurry
  2. temperatureThe reaction was heated
  3. temperatureto reflux for 18 h
  4. temperaturethe reaction was heated
  5. temperatureto reflux for six hours
  6. temperatureThe reaction cooled to room temperature
  7. temperaturethe reaction was heated
  8. temperatureto reflux for 18 h
  9. temperatureThe reaction was cooled to room temperature
  10. temperaturethe reaction was heated
  11. temperatureto reflux for six hours
  12. temperatureThe reaction was cooled to room temperature
  13. filtrationthe precipitated off-white solid was filtered
  14. washwashed with water (3×40 mL)
  15. customThe solid was dried under vacuum

Sources & evidence

ORD record
ord-bbf41be1159c4710afc0f4542e8c4658
Source dataset
uspto-grants-2012_10
Patent number
US08283354B2

Reaction notes

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