4-Chloro-3-fluoropyridine

Light yellow liquid

A 30-gal Hastelloy reactor under nitrogen is charged with 2.5 kg (25.8 mole) of 3-fluoropyridine, 3.4 kg (29.6 mole, 1.2 equiv.) of tetramethylethylenediamine (TMEDA) and 20 L of methyl tert-butyl ether (MTBE). The solution is cooled to-50°C. A total of 15.5 L (12.6 L, 29.6 mole, 1.15 equiv.) of 1.9 M lithium diisopropylamide (LDA) solution (heptane/THF/ethylbenzene) is added over a period of 24 min while maintaining a temperature of-40 to-48 °C. The light-brown suspension is stirred for 50 rnin at-44 to-48°C. A solution of 7 kg (29.6 mole, 1.15 equiv.) of hexachloroethane in 20 L of MTBE is added over a period of 48 min while maintaining a temperature of-40 to-46°C. After stirring for 20 min at-40°C, the reaction is warmed to 0°C, then quenched into a reactor that contained 54 L of cold water. After stirring at 20-25°C for 20 min, the mixture is filtered through Celite to break a minor emulsion. The layers are separated. The aqueous layer is extracted with 5 L of MTBE. The organic layers are combined, then extracted with portions (1 x 21 L, 3 x 13 L) of 2 N HCl. The acidic aqueous phases are combined, partitioned with 16 L of MTBE, then basified to pH 6.19 by adding 6.5 kg of 50percent NaOH while maintaining a temperature of 15- 20 °C. The layers are separated. The aqueous phase is extracted with 10 L of MTBE. The combined organic phase is dried over 3.0 kg of sodium sulfate, then filtered and concentrated (56°C, 575 mbar during most of the concentration, 400 mbar for final concentration) to give 3.7 kg of 4-chloro-3-fluoropyridine, as a brown liquid, 2.4 kg corrected for 31. 2percent solvent by NMR and 95. 5percent purity by HPLC, 70.2percent yield.

Molecular Weight:131.53
XLogP3:1.6
Hydrogen Bond Acceptor Count:2
Exact Mass:130.9938050
Monoisotopic Mass:130.9938050
Topological Polar Surface Area:12.9
Heavy Atom Count:8
Complexity:78.8
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes