Phosphorus oxychloride → 4-Chloro-7-methoxy-quinazoline

HRID 1811050Notes

Reaction equation

HRID 1811050 reaction equation
[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([C:7](O)=[N:8][CH:9]=[N:10]2)=[CH:5][CH:4]=1.P(Cl)(Cl)([Cl:16])=O>>[Cl:16][C:7]1[C:6]2[C:11](=[CH:12][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[N:10]=[CH:9][N:8]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178487763HCID 178487763, compound

Product 1

HCID 189250784-Chloro-7-methoxy-quinazolineYield 99.1%

Procedure

Step 2 A suspension of 7-methoxyquinazolin-4-ol (400 mg, 2.271 mmol) in phosphorus oxychloride (7 mL, 75 mmol) was heated at reflux for 3 h. The solution was concentrated and the residue was suspended in EtOAc and stirred on an ice bath with NaHCO3 (aq) until all the solid was dissolved and gas evolution ceased. The layers were separated and the organic phase was dried and concentrated to provide 4-chloro-7-methoxyquinazoline as a light yellow-tan solid (438 mg, 99%). 1H NMR (400 MHz, chloroform-d) δ 8.94 (1 H, s), 8.15 (1 H, d, J=9.7 Hz), 7.29-7.37 (2 H, m), 4.00 (3 H, s).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 3 h
  3. concentrationThe solution was concentrated
  4. dissolutionwas dissolved
  5. customThe layers were separated
  6. customthe organic phase was dried
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-6e27e0dba65e41c788ae4ac3843e316e
Source dataset
uspto-grants-2013_01
Patent number
US08362065B2

Reaction notes

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