4-Methoxyphenol → 4-(4-Methoxyphenoxy)quinazoline

HRID 1876104Notes

Reaction equation

HRID 1876104 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][CH:4]=1.Cl[C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[N:14]=[CH:13][N:12]=1.[H-].[Na+]>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][C:11]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[N:14]=[CH:13][N:12]=2)=[CH:5][CH:4]=1

Participants

5

Reactant 3

HCID 90154-MethoxyphenolHCID 24758Sodium hydrideHCID 788644-Chloroquinazoline

Product 1

HCID 238485294-(4-Methoxyphenoxy)quinazolineYield 89%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 4-methoxyphenol (75 mg, 0.60 mmol) and 4-chloro-quinazoline (125 mg, 76 mmol) in 3 mL of DMF was added sodium hydride (60% oil suspension, 30 mg, 0.75 mmol) at 0° C., then the reaction mixture was allowed to warm to room temperature and stirred for 5 h. The reaction was quenched by adding 50 uL of water and diluted with 25 mL of ethyl acetate. It was washed with water (25 mL×3), saturated NaCl, dried over anhydrous MgSO4, filtered and concentrated. The residue was purified by chromatography (25% ethyl acetate/hexanes) to give the title compound (134 mg, 0.53 mmol, 89%). 1H NMR (CDCl3): 8.78 (s, 1H), 8.38 (m, 1H), 7.89-8.02 (m, 2H), 7.67 (m, 1H), 7.19 (m, 1H), 7.00 (m, 1H), 3.86 (s, 3H).

Workup

  1. customThe reaction was quenched
  2. additionby adding 50 uL of water
  3. additiondiluted with 25 mL of ethyl acetate
  4. washIt was washed with water (25 mL×3), saturated NaCl
  5. dry with materialdried over anhydrous MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by chromatography (25% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-7c493029dac64004aacd279796bd264f
Source dataset
uspto-grants-2012_11
Patent number
US08309562B2

Reaction notes

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