Hydrochloric Acid → (7-(Benzyloxy)-6-methoxy-4-oxoquinazolin-3(4H)-yl)methyl pivalate

HRID 1384664Notes

Reaction equation

HRID 1384664 reaction equation
[H-].[Na+].[CH2:3]([O:10][C:11]1[CH:20]=[C:19]2[C:14]([C:15](=[O:21])[NH:16][CH:17]=[N:18]2)=[CH:13][CH:12]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[C:22]([O:28][CH2:29]Cl)(=[O:27])[C:23]([CH3:26])([CH3:25])[CH3:24].Cl.CN([CH:35]=[O:36])C>C(OCC)(=O)C>[CH2:3]([O:10][C:11]1[CH:20]=[C:19]2[C:14]([C:15](=[O:21])[N:16]([CH2:29][O:28][C:22](=[O:27])[C:23]([CH3:26])([CH3:25])[CH3:24])[CH:17]=[N:18]2)=[CH:13][C:12]=1[O:36][CH3:35])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 87885Chloromethyl pivalateHCID 1357631107-(Benzyloxy)-3,4-dihydroquinazolin-4-one

Product 1

HCID 10834555(7-(Benzyloxy)-6-methoxy-4-oxoquinazolin-3(4H)-yl)methyl pivalateYield 84%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Sodium hydride (1.44 g of a 60% suspension in mineral oil, 36 mmol) was added in portions over 20 minutes to a solution of 7-benzyloxy-3,4-dihydroquinazolin-4-one (8.46 g, 30 mmol), (prepared as described for the starting material in Example 70), in DMF (70 ml) and the mixture stirred for 1.5 hours. Chloromethyl pivalate (5.65 g, 37.5 mmol) was added dropwise and the mixture stirred 2 hours at ambient temperature. The mixture was diluted with ethyl acetate (100 ml) and poured onto ice/water (400 ml) and 2M hydrochloric acid (4 ml). The organic layer was separated and the aqueous layer extracted with ethyl acetate, the combined extracts were washed with brine, dried (MgSO4) and the solvent removed by evaporation. The residue was triturated with a mixture of ether and petroleum ether, the solid was collected by filtration and dried under vacuum to give 7-benzyloxy-6-methoxy-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (10 g, 84%). 1H NMR Spectrum: (DMSOd6) 1.11(s, 9H); 3.89(s, 3H); 5.3(s, 2H); 5.9(s, 2H); 7.27(s, 1H); 7.35(m, 1H); 7.47(t, 2H); 7.49(d, 2H); 7.51(s, 1H); 8.34(s, 1H)

Workup

  1. custom(prepared
  2. stirringthe mixture stirred 2 hours at ambient temperature
  3. customThe organic layer was separated
  4. extractionthe aqueous layer extracted with ethyl acetate
  5. washthe combined extracts were washed with brine
  6. dry with materialdried (MgSO4)
  7. customthe solvent removed by evaporation
  8. customThe residue was triturated with a mixture of ether and petroleum ether
  9. filtrationthe solid was collected by filtration
  10. customdried under vacuum

Sources & evidence

ORD record
ord-54cc70e853944046ab9bfdab06881587
Source dataset
uspto-grants-2001_07
Patent number
US06258951B1

Reaction notes

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