Dichloromethane → Methyl 2,4-dichloroquinazoline-7-carboxylate

HRID 1672444Notes

Reaction equation

HRID 1672444 reaction equation
O[C:2]1[N:11]=C(O)[C:9]2[C:4](=[CH:5][C:6]([C:13]([O:15][CH3:16])=[O:14])=[CH:7][CH:8]=2)[N:3]=1.O=P(Cl)(Cl)Cl.P(Cl)(Cl)(Cl)(Cl)[Cl:23].C([O-])(O)=O.[Na+].[CH2:33]([Cl:35])Cl>O>[Cl:23][C:2]1[N:11]=[C:33]([Cl:35])[C:9]2[C:4](=[CH:5][C:6]([C:13]([O:15][CH3:16])=[O:14])=[CH:7][CH:8]=2)[N:3]=1

Participants

7

Reactant 5

HCID 6344Dichloromethane3×HCID 24813Phosphorus oxychlorideHCID 24819Phosphorus pentachlorideHCID 516892Sodium BicarbonateHCID 178497303HCID 178497303, compound

Product 1

HCID 40152337Methyl 2,4-dichloroquinazoline-7-carboxylate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a 250 mL flask charged with methyl 2,4-dihydroxyquinazoline-7-carboxylate was added POCl3 (76 mL), PCl5 (12.1 g, 58.1 mmol), and the suspension heated at reflux overnight under nitrogen. In morning a dark orange solution has formed. The POCl3 was removed and the residue azeotroped with toluene to yield an orange solid that was taken into DCM (50 mL) and added slowly to stirred satd NaHCO3 (300 mL). The bi-phasic solution was then diluted with DCM (100 mL) and water (30 mL) and stirred for 1 hour at room temp. DCM (500 mL) was added and the mix transferred to a sep-funnel. The DCM layer was removed along with a large amount of ppt. The aq. was extracted with DCM (3×100 mL) and the combined organics dried over MgSO4, filtered and stripped to a orange solid that was purified by Biotage 65 flash chromatography eluting with DCM −3% MeOH/DCM over 3.5 L to reveal the title compound as a white solid, 4.4 g, 59%. 1H NMR (400 MHz, DMSO-D6) δ ppm 8.47 (1H, d, J=1.01 Hz) 8.43 (1H, d, J=8.84 Hz) 8.29 (1H, dd, J=8.72, 1.64 Hz) 3.96 (3H, s); MS (API+) for C10H6N2Cl2O2 m/z 257.0 (M+H)+.

Workup

  1. temperaturethe suspension heated
  2. temperatureat reflux overnight under nitrogen
  3. customIn morning a dark orange solution has formed
  4. customThe POCl3 was removed
  5. customthe residue azeotroped with toluene
  6. customto yield an orange solid that
  7. additionadded slowly
  8. customthe mix transferred to a sep-funnel
  9. customThe DCM layer was removed along with a large amount of ppt
  10. extractionThe aq. was extracted with DCM (3×100 mL)
  11. dry with materialthe combined organics dried over MgSO4
  12. filtrationfiltered
  13. customthat was purified by Biotage 65 flash chromatography
  14. washeluting with DCM −3% MeOH/DCM over 3.5 L

Sources & evidence

ORD record
ord-8e40c95267f2469380e7e41b516db7a4
Source dataset
uspto-grants-2011_08
Patent number
US07998978B2

Reaction notes

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