Sodium hydride → HCID 28888108, compound

HRID 336759Notes

Reaction equation

HRID 336759 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([CH3:11])[C:9]=1[OH:10])[CH:5]=[O:6].[H-].[Na+].Br[CH2:15][CH2:16][O:17][CH3:18]>CN(C=O)C>[CH3:18][O:17][CH2:16][CH2:15][O:10][C:9]1[C:8]([CH3:11])=[CH:7][C:4]([CH:5]=[O:6])=[CH:3][C:2]=1[CH3:1]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 752223,5-Dimethyl-4-hydroxybenzaldehydeHCID 809722-Bromoethyl methyl ether

Product 1

HCID 28888108HCID 28888108, compoundYield 75.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3,5-dimethyl-4-hydroxy benzaldehyde (2.0 g, 13.33 mmol) in DMF was added NaH (640 mg, 16.0 mmol, 60% in oil) and the mixture was stirred for 1 h at room temperature. A solution of 1-bromo-2-methoxy ethane (1.85 g, 13.33 mmol) was added and the mixture was stirred for 72 h at room temperature. The reaction mixture was quenched by addition of saturated NH4Cl solution and diluted with water. The product was extracted with ethyl acetate. The combined organic layers were washed with water, brine and dried over Na2SO4. Upon removal of solvent, it gave 2.1 g of 4-(2-methoxy ethoxy)-3,5-dimethyl benzaldehyde (76 yield). To a solution of 2-amino-4,6-dimethoxy-benzamide (200 mg, 1.02 mmol) and 4-(2-methoxy ethoxy)-3,5-dimethyl benzaldehyde (212 mg, 1.02 mmol) in N,N-dimethyl acetamide (10 mL), NaHSO3 (199 mg, 1.12 mmol) and p-TSA (22 mg, 0.102 mmol) were added and the reaction mixture was heated at 150° C. for 3 h. Cooled to room temperature and the solvent was evaporated under reduced pressure. The residue was diluted with water and the solid was collected to give the crude product. The crude product was purified by chromatography using 2% MeOH in CH2Cl2 to give 5,7-dimethoxy-2-(4-(2-methoxyethoxy)-3,5-dimethylphenyl)quinazolin-4(3H)-one (170 mg, 43%). Selected data: MS (ES) m/z: 385.10; MP 201-202° C.

Workup

  1. stirringthe mixture was stirred for 72 h at room temperature
  2. customThe reaction mixture was quenched by addition of saturated NH4Cl solution
  3. additiondiluted with water
  4. extractionThe product was extracted with ethyl acetate
  5. washThe combined organic layers were washed with water, brine
  6. dry with materialdried over Na2SO4
  7. customUpon removal of solvent, it

Sources & evidence

ORD record
ord-0bb95651284e49c6bb02c66f00a76130
Source dataset
uspto-grants-2014_11
Patent number
US08889698B2

Reaction notes

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