Hydrochloric Acid → 5-hydroxy-7-methoxy-3-(4-methoxyphenyl)-4(3H)-quinazolinone

HRID 130334Notes

Reaction equation

HRID 130334 reaction equation
C[O:2][C:3]1[CH:12]=[C:11]([O:13][CH3:14])[CH:10]=[C:9]2[C:4]=1[C:5](=[O:23])[N:6]([C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=1)[CH:7]=[N:8]2.[Cl-].[Li+].O.Cl>CC(N(C)C)=O>[OH:2][C:3]1[CH:12]=[C:11]([O:13][CH3:14])[CH:10]=[C:9]2[C:4]=1[C:5](=[O:23])[N:6]([C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=1)[CH:7]=[N:8]2

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 433294Lithium ChlorideHCID 116881915,7-Dimethoxy-3-(4-methoxyphenyl)quinazoline-4-one

Product 1

HCID 115874645-hydroxy-7-methoxy-3-(4-methoxyphenyl)-4(3H)-quinazolinoneYield 48%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
135 °C

Procedure

A suspension of 5,7-dimethoxy-3-(4-methoxyphenyl)-4(3H)-quinazolinone (2.40 g, 7.68 mmol), as prepared in Example 18 or 19 and anhydrous lithium chloride (6.51 g, 153.6 mmol) in anhydrous dimethylacetamide (51.2 mL) was warmed to 135° C. After 3 to 5 min the trimethoxy compound goes into solution, then after approximately 10 min a voluminous precipitate formed. The precipitate redissolved after 20 min and the resulting solution was stirred at 135° C. for an additional 2.5 h. Upon cooling to room temperature, the reaction was poured into water (100 mL) and acidified with 1.0N HCl which gave a white precipitate. The mixture was extracted with dichloromethane (3×). The combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated in vacuo to remove the methylene chloride, leaving a white precipitate in dimethylacetamide. Filtration provided 1.10 g (48% yield) of 5-hydroxy-7-methoxy-3-(4-methoxyphenyl)-4(3H)-quinazolinone, as a white solid.

Workup

  1. customafter approximately 10 min a voluminous precipitate formed
  2. dissolutionThe precipitate redissolved after 20 min
  3. temperatureUpon cooling to room temperature
  4. customgave a white precipitate
  5. extractionThe mixture was extracted with dichloromethane (3×)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto remove the methylene chloride
  11. customleaving a white precipitate in dimethylacetamide
  12. filtrationFiltration

Sources & evidence

ORD record
ord-b5e439761e374003a3d2dd17bd5a96ec
Source dataset
uspto-grants-2008_06
Patent number
US07381730B2

Reaction notes

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