Reaction #430065

Reaction equation

6-chloroquinoline

iodine

triethylamine

fluorine

fluorine

→

2-fluoro-6-chloroquinoline

Yield 93.0%

Solvents

—

CF2ClCFCl2

sodium metabisulfite

Conditions

Workup

1. 1
   Otherfitted with a drying tube
2. 2
   Extractionextracted with dichloromethane
3. 3
   OtherThe organic extracts were dried
4. 4
   Otherevaporated to a brown solid (1.03 g)

Procedure

A solution containing 6-chloroquinoline (1.0 g, 6.1 mmol), iodine (1.55 g, 6.1 mmol) and triethylamine (0.62 g, 6.2 mmol) in CF2ClCFCl2 (30 ml) was placed in a fluorination apparatus fitted with a drying tube filled with soda lime. Elemental fluorine (7 mmol) as a 10% mixture in dry nitrogen was then passed through the stirred solution using narrow bore PTFE tubing at ca. 15 ml/min. After the fluorine had been added the solution was poured into 10% aqueous sodium metabisulfite solution (30 ml) and extracted with dichloromethane. The organic extracts were dried and evaporated to a brown solid (1.03 g). GC/MS analysis showed a 79% conversion of starting material. Column chromatography on silica gel with dichloromethane as eluant gave 2-fluoro-6-chloroquinoline (0.82 g, 93%), RF 0.78 (CH2Cl2); δH (400 MHz CDCl3, Me4Si) 7.12 ppm (1H, d d, JH3,H4 8.8, JH3,F 2.8, H-3), 7.67 (1H, d d, JH7,H8 9.2, JH5,H7 2.4, H-7), 7.82 (1H, d, JH5,H7 2.4, H-5), 7.87 (1H, d, JH7,H8 9.0, H-8), 8.16 (1H, d d, JH3,H4 =JH4,F 8.8, H-4);δC (100 MHz, CDCl3, Me4Si) 111.1 ppm (d, 2J 42.3, C-3), 126.3 (s, C-5), 127.3 (s, C-4a), 129.6 (s, C-8), 131.4 (s, C-7), 131.9 (s, C-6) 141.0 (d,3J 9.9, C-4), 144.1 (d 3J 16.8, C-8a), 161.2 (d, 1J 243.8, C-2); δF (235 MHz, CDC13, CFCl3) -61.5 ppm (s); m/z (E1+) 181 (M+, 100%), 183 (M+, 32), 146 (34), 126 (11).

Source