Phosphorus oxychloride → 4-Chloro-6-(trifluoromethyl)quinazoline

Preparation D3, Step 3: A suspension of 6-(trifluoromethyl)quinazolin-4-ol (10.41 g, 48.4 mmol) in phosphorous oxychloride (100 mL) was heated at reflux for 3 h, during which time a clear, amber solution was observed. The solution was cooled to room temperature, concentrated in-vacuo, and stripped 3× from 150 mL methylene chloride to remove any remaining phosphorous oxychloride. The residue was partitioned between EtOAc and saturated sodium bicarbonate (1:1, 300 mL), and the mixture was stirred until gas evolution ceased. The layers were separated, the organic phase was washed successively with saturated sodium bicarbonate and brine, the combined aqueous phases were extracted with EtOAc (50 mL), and the combined organic phases were dried over sodium sulfate then concentrated in-vacuo. The residue was purified over silica gel, eluting with 25% EtOAc/Heptane, to yield 8.14 g of 4-chloro-6-(trifluoromethyl)quinazoline as a white solid. MS (ES+)=233, 235 (M+H+).

1. temperaturewas heated
2. temperatureat reflux for 3 h, during which time a clear, amber solution
3. concentrationconcentrated in-vacuo
4. customto remove any remaining phosphorous oxychloride
5. customThe residue was partitioned between EtOAc and saturated sodium bicarbonate (1:1, 300 mL)
6. customThe layers were separated
7. washthe organic phase was washed successively with saturated sodium bicarbonate and brine
8. extractionthe combined aqueous phases were extracted with EtOAc (50 mL)
9. dry with materialthe combined organic phases were dried over sodium sulfate
10. concentrationthen concentrated in-vacuo
11. customThe residue was purified over silica gel
12. washeluting with 25% EtOAc/Heptane

ORD record

ord-d970cb143f294f028e2673955fef4a33

Source dataset

uspto-grants-2009_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07482335B2