Phosphorus oxychloride → 2,7-Dichloroquinazoline

Temperature

110 °C

In a 250 mL three neck round bottom flask, 7-chloroquinazolin-2-ol (19 g, 105.55 mmol) was suspended in freshly distilled POCl3 (190 mL) at rt. The resulting suspension was heated to 110° C. for 4 h. On completion of reaction, the reaction mixture was cooled to rt and concentrated under reduced pressure. The residue obtained was diluted with ethyl acetate (200 mL) and cold water (200 mL). The organic layer was separated and the aqueous phase was re-extracted with ethyl acetate (500 mL×2). The combined EtOAc extract was washed with brine and concentrated under reduced pressure. The residue (pale brown) obtained was purified by silica gel (60-120 mesh) column chromatography and gradient elution with 12-20% ethyl acetate-hexanes gave 2,7-dichloroquinazoline as a pale yellow solid. Yield: 7 g (33.5%). LCMS (ESI, m/z): 199 (M+1)+.

1. customOn completion of reaction
2. temperaturethe reaction mixture was cooled to rt
3. concentrationconcentrated under reduced pressure
4. customThe residue obtained
5. customThe organic layer was separated
6. extractionthe aqueous phase was re-extracted with ethyl acetate (500 mL×2)
7. extractionThe combined EtOAc extract
8. washwas washed with brine
9. concentrationconcentrated under reduced pressure
10. customThe residue (pale brown) obtained
11. customwas purified by silica gel (60-120 mesh) column chromatography and gradient elution with 12-20% ethyl acetate-hexanes

ORD record

ord-9a38446e4a87436d8a61d7afd7a6b2b0

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09303028B2