6-Bromo-8-fluoroquinoline

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) (52 ml, 720 mmol) to give a thick grey suspension. This was heated to 110 A solution of concentrated H2504 (0.63 ml, ii .82 mmoi) in H20 (0.48 ml, 26.6 mmoi) was treated with 3-Nitrohenzenesulfonic acid, sodium salt ( 0.48g. 2.132 nrniol) and glycerol (0.516 ml. 706 mmoi) to give a thick grey suspension, the mixture was heated to 110 °C. 4-Bromo2fluoroaniline was added portion wise over 10 mm, during which the temperature rose to 95 °C. The reaction was heated to 140 °C and stirred overnight. The reaction mixture was cooled and then poured into water and basified to pH 7 with aqueous ammonia. The brown precipitated that formed was collected by filtration and partially dried. This solid (0.63 g) was purified by flash column chromatography givethe 6-bromo-8-fluoroquinohne (04 g, 1770 mmoi, 88 percent yield) compound.Glycerol (14.5 g, 158 mmol) And the catalyst sodium 3-nitrobenzenesulfonate (14.2 g, 63 mmol) were added to the sulfuric acid Aqueous solution (20 mL of concentrated sulfuric acid + 15 mL of water), The mixture was heated to 110 ° C and 2-fluoro-4-bromoaniline C-1 (10 g, 52.6 mmol) was added slowly and stirred at 140 ° C overnight. After dropping to room temperature, pour into crushed ice, adjust the pH to about 8 with concentrated aqueous ammonia, extract with ethyl acetate, wash with water, Washed with saturated saline, dried over anhydrous sodium sulfate, filtered and evaporated to dryness. The crude product was purified by column chromatography to obtain 9.65 g of white solid compound C-2, yield 81.2percent5.00 g (26.3 mmol) of 4-bromo-2-fluoroaniline, 5.31 g (57.89 mmol) glycerol and 9.89 g (43.94 mmol) of 3-nitrophenylsulfonic acid-sodium salt were prepared and homogenized. Then 25 ml of 70percent sulfuric acid was added dropwise. The mixture was stirred overnight at 135°C. The cooled black reaction mixture was made alkaline, cautiously and with ice cooling, with 50percent sodium hydroxide solution, and then filtered on a large bed of silica gel and kieselguhr. It was washed again with water and ethyl acetate. The phases collected were combined, then the organic phase was separated. The aqueous phase that remained was then extracted with ethyl acetate (2x). Then the organic phases thus obtained and the phase already separated previously were combined. It was dried over magnesium sulfate and the volatile components were removed in a rotary evaporator. The residue was finally purified by MPLC (Puriflash Analogix: 4OM: isohexane / ethyl acetate = 4 / 1). We obtained 3.56 g (60percent of theor.) of the target compound. IH-NMR (400 MHz, DMSO-DIntermediate 16-Bromo-8-fluoroquinoline 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, 97percent). LCMS RT=2.87 min, ES+ve m/z 226/228 [M+H]Intermediate 3

Molecular Weight:226.04
XLogP3:2.9
Hydrogen Bond Acceptor Count:2
Exact Mass:224.95894
Monoisotopic Mass:224.95894
Topological Polar Surface Area:12.9
Heavy Atom Count:12
Complexity:165
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes