Benzyl Alcohol → 7-(Benzyloxy)-3,4-dihydroquinazolin-4-one

HRID 1723719Notes

Reaction equation

HRID 1723719 reaction equation
[CH2:1]([OH:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].F[C:12]1[CH:21]=[C:20]2[C:15]([C:16](=[O:22])[NH:17][CH:18]=[N:19]2)=[CH:14][CH:13]=1>CN(C)C=O>[CH2:1]([O:8][C:12]1[CH:21]=[C:20]2[C:15]([C:16](=[O:22])[NH:17][CH:18]=[N:19]2)=[CH:14][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 244Benzyl AlcoholHCID 24758Sodium hydrideHCID 1353984967-Fluoroquinazolin-4(3H)-one

Product 1

HCID 1357631107-(Benzyloxy)-3,4-dihydroquinazolin-4-oneYield 93.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of benzyl alcohol (5.27 g, 48.7 mmol) in N,N-dimethylformamide (12 mL) was cooled to 0° C. prior to the portion-wise addition of sodium hydride (60% dispersion in mineral oil, 1.95 g, 48.7 mmol). This mixture was warmed to room temperature and stirred for 30 minutes before being cooled to 0° C. followed by the addition of a solution of the product from Step 1 (2.0 g, 12 mmol) in N,N-dimethylformamide (12 mL). After the addition, the reaction was warmed to 95° C. for 16 hours. After cooling to room temperature, the reaction was partitioned between EtOAc and H2O. The layers were separated and the precipitated solids in the organic layer were collected by filtration, washed with EtOAc and air dried. A second crop of solids was collected and the filtrate washed with saturated sodium chloride solution, dried over sodium sulfate and concentrated to provide a third crop of solids. Combination of the solids and drying to constant weight afforded 2.82 g (93%) of 7-(benzyloxy)quinazolin-4(3H)-one as a tan solid. MS 253.3 (ES+).

Workup

  1. temperaturebefore being cooled to 0° C.
  2. additionAfter the addition
  3. temperaturethe reaction was warmed to 95° C. for 16 hours
  4. temperatureAfter cooling to room temperature
  5. customthe reaction was partitioned between EtOAc and H2O
  6. customThe layers were separated
  7. filtrationthe precipitated solids in the organic layer were collected by filtration
  8. washwashed with EtOAc and air
  9. customdried
  10. customA second crop of solids was collected
  11. washthe filtrate washed with saturated sodium chloride solution
  12. dry with materialdried over sodium sulfate
  13. concentrationconcentrated
  14. customto provide a third crop of solids
  15. customCombination of the solids and drying to constant weight

Sources & evidence

ORD record
ord-d14aa6ca8c7e469d8a03232838deb664
Source dataset
uspto-grants-2009_02
Patent number
US07485641B2

Reaction notes

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