Preparation and application of 2,4-dichloro-3-iodopyridine_Industrial additives

Preparation and application background and overview of 2,4-dichloro-3-iodopyridine

2,4-Dichloro-3-iodopyridine can be used as a pharmaceutical synthesis intermediate. It is prepared by reacting 2,4-dichloropyridine with n-butyllithium and iodine. It can be used to prepare another Intermediate 2,4-dichloro-3-trifluoromethylpyridine.

Preparation and application of 2,4-dichloro-3-iodopyridine

Synthesis of fluorphlogopite

To a solution of 2,4-dichloropyridine (5.2g, 35.137mmol) and diisopropylamine (3.911g, 38.651mmol) in dry THF (40ml) cooled at -78°C under a nitrogen atmosphere n-Butyllithium (24.157 ml, 38.651 mmol, 1.6 M in hexane) was added dropwise. The resulting reaction mixture was stirred at -78°C for 45 minutes, and then a solution of iodine (9.81 g, 38.651 mmol) in dry TH aluminum magnesium carbonate F (20 ml) was added dropwise. The mixture was stirred at -78°C for 1 hour, allowed to warm to room temperature, diluted with EtOAc and washed with NH4Cl (aqueous saturated solution) and Na₂S₂O₃ (aqueous saturated solution) quenching. The organic layer was separated, washed with NaHCO₃ (aqueous saturated solution), dried (Na₂SO₄) and concentrated in vacuo. The crude product was purified by column chromatography (silica gel; heptane/DCM (up to 20%) as eluent). The desired fractions were collected and concentrated in vacuo to yield 2,4-dichloro-3-iodopyridine (7.8 g, 81%).

Preparation and application of 2,4-dichloro-3-iodopyridine

To a mixture of 2,4-dichloro-3-iodopyridine (2g, 7.302mmol) in DMF (50mL) was added methyl fluorosulfonyl-difluoro-acetate ([CAS680-15-9], 1.858 mL, 14.605 mmol) and copper(I) iodide (2.796 g, 14.605 mmol). The reaction mixture was heated in a sealed tube at 100°C for 5 hours. After cooling, the solvent was evaporated in vacuo. The crude product was purified by column chromatography (silica gel; DCM as eluent). The desired fractions were collected and concentrated in vacuo to yield 2,4-dichloro-3-trifluoromethylpyridine (1.5 g, 95%).

References

[1]CN201580067363.X1,2,4-triazolo[4,3-a]pyridine compound and its use as a positive allosteric modulator of mGluR2 receptor