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

HRID 495387
Notes
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Reaction equation

HRID 495387 reaction equation
[H-].[Na+].[CH2:3]([O:10][C:11]1[CH:20]=[C:19]2[C:14]([CH2:15][NH:16][C:17](=O)[NH:18]2)=[CH:13][C:12]=1[O:22][CH3:23])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[C:24]([O:30][CH2:31]Cl)(=[O:29])[C:25]([CH3:28])([CH3:27])[CH3:26].Cl.CN(C=[O:38])C>C(OCC)(=O)C.O>[CH2:3]([O:10][C:11]1[CH:20]=[C:19]2[C:14]([C:15](=[O:38])[N:16]([CH2:31][O:30][C:24](=[O:29])[C:25]([CH3:28])([CH3:27])[CH3:26])[CH:17]=[N:18]2)=[CH:13][C:12]=1[O:22][CH3:23])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 87885Chloromethyl pivalateHCID 545382477-Benzyloxy-6-methoxy-3,4-dihydroquinazolinone

Product 1

HCID 10834555(7-(Benzyloxy)-6-methoxy-4-oxoquinazolin-3(4H)-yl)methyl pivalate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

Sodium hydride (60% dispersion in mineral oil, 1.44 g) was added portionwise during 20 minutes to a solution of 7-benzyloxy-6-methoxy-3,4-dihydroquinazolinone (8.46 g) in DMF (70 ml) and the mixture was stirred for 1.5 hours. Chloromethyl pivalate (5.65 g) was added dropwise and the mixture was stirred at ambient temperature for 2 hours. The mixture was diluted with ethyl acetate (100 ml) and poured onto a mixture of ice and water (400 ml) containing 2N aqueous hydrochloric acid (4 ml). The organic layer was separated and the aqueous layer was extracted with ethyl acetate. The organic extract was washed with a saturated aqueous sodium chloride solution, dried over magnesium sulphate and evaporated. The residue was triturated under a mixture of petroleum ether (b.p. 60-80° C.) and diethyl ether. The solid so obtained was isolated and dried under vacuum to give 7-benzyloxy-6-methoxy-3-pivaloyloxymethyl-3,4dihydroquinazolin-4-one (10 g); 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. stirringthe mixture was stirred at ambient temperature for 2 hours
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted with ethyl acetate
  4. extractionThe organic extract
  5. washwas washed with a saturated aqueous sodium chloride solution
  6. dry with materialdried over magnesium sulphate
  7. customevaporated
  8. customThe residue was triturated under a mixture of petroleum ether (b.p. 60-80° C.) and diethyl ether
  9. customThe solid so obtained
  10. customwas isolated
  11. customdried under vacuum

Sources & evidence

ORD record
ord-e13d259b954e451e88712b48562bbc3e
Source dataset
uspto-grants-2005_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US06939866B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes