Ammonia → 6-Bromo-8-fluoroquinoline

Temperature

85 °C

A solution of concentrated sulphuric acid (63 ml, 820 mmol) in water (49.4 ml) was treated with sodium 3-nitro-benzenesulfonate (commercially available, for example, from Aldrich) (47.9 g, 213 mmol) and glycerol (commercially available, for example, from Fluka and/or Aldrich) (52 ml, 720 mmol) to give a thick grey suspension. This was heated to 110° C. (internal temperature was 85° C.). 4-Bromo-2-fluoroaniline (commercially available, for example, from Fluorochem and/or Aldrich) (38 g, 200 mmol) was added over 10 min in portions, during which the internal temperature rose to 95° C. The reaction was heated to 140° C. (internal temperature was 133° C.) and stirred overnight. The reaction mixture was cooled and then poured into water (1000 ml) and basified to pH 7 with aqueous ammonia (0.88 s.g, approximately 190 ml). The brown precipitate that formed was collected by filtration and partially dried. This solid (63 g) was loaded onto a column of silica (1500 ml) and eluted with EtOAc to give the title compound as a light brown solid (43.8 g, 97%). LCMS RT=2.87 min, ES+ve m/z 226/228 [M+H]+.

1. customwas added over 10 min in portions, during which
2. customrose to 95° C
3. temperatureThe reaction was heated to 140° C. (internal temperature was 133° C.)
4. temperatureThe reaction mixture was cooled
5. customThe brown precipitate that formed
6. filtrationwas collected by filtration
7. custompartially dried
8. washeluted with EtOAc

ORD record

ord-ed59029f80334d90aa20cf64a197c30d

Source dataset

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07884114B2