Phosphorus oxychloride → 4-Chloroquinazoline

Temperature

140 °C

A mixture of 4-hydroxyquinazoline (2.56 g, 17.5 mmol) and POCl3 (8.0 mL, 88 mmol) was stirred at 140° C. (oil bath) for 10 min. The homogeneous light amber solution was then allowed to cool to rt before concentrating under reduced pressure at 70° C. The translucent residue was dissolved in DCM (25 mL), and the homogeneous yellow solution was partitioned with ice and 1 M NaHCO3 to pH ˜6 (paper) (˜20 mL aq layer). The organic layer was dried twice (Na2SO4), filtered through a 0.22 micron filter, and concentrated under reduced pressure (bath <40° C.) to provide the title compound as a yellow solid (2.53 g, 88%). 1H-NMR (300 MHz, CDCl3) δ 9.07 (s, 1H), 8.30 (ddd, 1H), 8.11 (m, 1H), 8.00 (m, 1H), 7.77 (m, 1H).

1. temperatureto cool to rt
2. concentrationbefore concentrating under reduced pressure at 70° C
3. dissolutionThe translucent residue was dissolved in DCM (25 mL)
4. customthe homogeneous yellow solution was partitioned with ice and 1 M NaHCO3 to pH ˜6 (paper) (˜20 mL aq layer)
5. dry with materialThe organic layer was dried twice (Na2SO4)
6. filtrationfiltered through a 0.22 micron
7. filtrationfilter
8. concentrationconcentrated under reduced pressure (bath <40° C.)

ORD record

ord-e99d6cc38e3244d0a799690189541de2

Source dataset

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08071768B2