Phosphorus oxychloride → 8-Bromo-4-chloroquinazoline
Reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][N:8]=[C:7]2O.P(Cl)(Cl)([Cl:15])=O>>[Br:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][N:8]=[C:7]2[Cl:15]Participants
Procedure
A suspension of 8-bromoquinazolin-4-ol (410 mg, 1.822 mmol) in phosphorous oxychloride (15.000 mL, 161 mmol) was heated to reflux. After refluxing 45 min, a clear, amber solution was observed. Refluxed an additional 30 min, concentrated in-vacuo, and concentrated 2× from methylene chloride to remove residual phosphorous oxychloride. The residue was taken up in ethyl acetate (50 mL), treated with the careful addition of saturated sodium bicarbonate, and this mixture was stirred for 5 minutes, until gas evolution had ceased. The layers were separated, the and the aqueous phase was extracted with ethyl acetate (20 mL). The combined organic phases were washed with saturated sodium bicarbonate, water, and saturated sodium chloride, dried over sodium sulfate, and concentrated in-vacuo to yield the title compound (442 mg, 1.815 mmol, 100% yield) as a tan powder which was used as-is in the next step.
Workup
- temperaturewas heated to reflux
- temperatureAfter refluxing 45 min
- temperatureRefluxed an additional 30 min
- concentrationconcentrated in-vacuo
- concentrationconcentrated 2× from methylene chloride
- customto remove residual phosphorous oxychloride
- additiontreated with the careful addition of saturated sodium bicarbonate
- customThe layers were separated
- extractionthe and the aqueous phase was extracted with ethyl acetate (20 mL)
- washThe combined organic phases were washed with saturated sodium bicarbonate, water, and saturated sodium chloride
- dry with materialdried over sodium sulfate
- concentrationconcentrated in-vacuo
Sources & evidence
- ORD record
- ord-5ee4b95c7da245499e4b71c859eb8922
- Source dataset
- uspto-grants-2009_10
- Patent number
- US07601844B2
Reaction notes
Loading…