Phosphorus tribromide → 4-Bromo-3-chloroquinoline

Temperature

0 °C

To a cooled suspension of 3-chloroquinolin-4(1H)-one (A275-1) (5.15 g, 28.7 mmol) in DMF (43.4 mL) at 0° C. was added phosphorous tribromide (2.77 mL, 29.5 mmol) dropwise over 3 min and then the mixture became orange homogenous mixture. After 4 min, yellow precipitates were formed and the yellow heterogeneous mixture was further stirred at 0° C. for 15 min. After 15 min, the cooling bath was removed and the yellow heterogeneous mixture was stirred at room temperature. After 15 h, the mixture was poured into ice water (300 mL) and stirred at 0° C. for 20 min. The mixture was then neutralized by the addition of 2 M NaOH solution (50 mL) until pH was >9 (pH paper). The resulting precipitate was collected by filtration, washed the solid with water (400 mL), and dried under high vacuum to give 4-bromo-3-chloroquinoline (A275-2) as off-white solid. 1H NMR (400 MHz, DMSO-d6) δ 8.96 (1H, s), 8.20 (1H, dd, J=8.2, 1.6 Hz), 8.12 (1H, dd, J=8.3, 0.9 Hz), 7.81-7.93 (2H, m); LCMS (ESI) m/z 242.0 [M+H (79Br)]+ and 243.9 [M+H (81Br)]+.

1. customyellow precipitates
2. customwere formed
3. waitAfter 15 min
4. customthe cooling bath was removed
5. stirringthe yellow heterogeneous mixture was stirred at room temperature
6. waitAfter 15 h
7. additionthe mixture was poured into ice water (300 mL)
8. stirringstirred at 0° C. for 20 min
9. additionThe mixture was then neutralized by the addition of 2 M NaOH solution (50 mL) until pH was >9 (pH paper)
10. filtrationThe resulting precipitate was collected by filtration
11. washwashed the solid with water (400 mL)
12. customdried under high vacuum

ORD record

ord-2d607bda4f6d4dbd9a5bffe7845acfeb

Source dataset

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09365522B2