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
