Phosphorus oxychloride → HCID 21075094, compound

HRID 1455352Notes

Reaction equation

HRID 1455352 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[N:15]=[CH:14][N:13]=[C:12]2O.O=P(Cl)(Cl)[Cl:22]>>[Cl:22][C:12]1[C:11]2[C:16](=[CH:17][CH:18]=[C:9]([C:4]3[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=3[O:2][CH3:1])[CH:10]=2)[N:15]=[CH:14][N:13]=1

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178489278HCID 178489278, compound

Product 1

HCID 21075094HCID 21075094, compound

Procedure

Preparation D6, Step 3. A suspension of 6-(2-methoxyphenyl)quinazolin-4-ol (250 mg, 0.99 mmol) in POCl3 (10 mL) was heated at reflux for 1 h, during which time a clear solution was observed. The mixture was cooled to room temperature, concentrated in-vacuo, then concentrated from methylene chloride (3×100 mL) to remove any remaining POCl3. The residue was partitioned between ethyl acetate (25 mL) and saturated NaHCO3 (30 mL), and the mixture was stirred until gas evolution ceased (10 min). The layers were separated, the organic phase was washed with saturated NaHCO3, water, and brine, dried over sodium sulfate, and concentrated in-vacuo. The residue was purified over silica gel, eluting with 1:3 ethyl acetate/heptane, to yield 217 mg of 4-chloro-6-(2-methoxyphenyl)quinazoline as a white solid. 1H NMR (500 MHz, CDCl3) δ ppm 9.03 (s, 1H), 8.36 (s, 1H), 8.19 (d, J=7.15 Hz, 1H), 8.10 (d, J=8.80 Hz, 1H), 7.42 (m, 2H), 7.10 (t, J=7.42 Hz, 1H), 7.04 (d, J=8.25 Hz, 1H), 3.86 (m, 3H).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 1 h, during which time a clear solution
  3. concentrationconcentrated in-vacuo
  4. concentrationconcentrated from methylene chloride (3×100 mL)
  5. customto remove any remaining POCl3
  6. customThe residue was partitioned between ethyl acetate (25 mL) and saturated NaHCO3 (30 mL)
  7. custom(10 min)
  8. customThe layers were separated
  9. washthe organic phase was washed with saturated NaHCO3, water, and brine
  10. dry with materialdried over sodium sulfate
  11. concentrationconcentrated in-vacuo
  12. customThe residue was purified over silica gel
  13. washeluting with 1:3 ethyl acetate/heptane

Sources & evidence

ORD record
ord-d1e564b1b3cf4c7d8a895909d6984d84
Source dataset
uspto-grants-2009_01
Patent number
US07482335B2

Reaction notes

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