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

HRID 2079259Notes

Reaction equation

HRID 2079259 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-073790d5f9e4496292d0a45cc7daa3ff
Source dataset
uspto-grants-2011_04
Patent number
US07928107B2

Reaction notes

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