preparation of 2,6-difluoro-4-iodopyridine_industrial additives

preparation background and overview of 2,6-difluoro-4-iodopyridine

2,6-difluoro-4-iodopyridine can be used as a pharmaceutical synthesis intermediate. 2,6-difluoropyridine can be used as the reaction raw material, and the intermediate 3-chloro can be generated under the action of n-butyllithium and iodine. hydroxypyridine-iodo-2,6-difluoropyridine is further reacted to prepare 2,6-difluoro-4-iodopyridine.

preparation of 2,6-difluoro-4-iodopyridine

step 1 of the preparation of 2,6-difluoro-4-iodopyridine:

add n-butyllithium (7.5 ml, 12 mmol, 1.6 m in hexanes) dropwise to diisopropylamine (1.7 ml, 12 mmol) in th iv at -78°c under nitrogen protection. to the solution in sodium borate f (10 ml), after 20 minutes, add 2,6-difluoropyridine (1.1 ml, 12 mmol) dropwise, after another 1 hour, maintain -78°c, and add iodine (3.2 g, 13.5 mmol) in thf (5 ml). the solution was allowed to warm to room temperature over 1 hour, washed with 10% aqueous na2so3 (10 ml), and extracted with ethyl acetate (50 ml). the organic extract was dried (na₂so₄), concentrated in vacuo, and the residue was recrystallized from petroleum ether to obtain 3-iodo-2,6-difluoropyridine ( 2.72g, 94%), colorless crystals, yield (2.72g, 94%), melting point 38-40°c.

preparation of 2,6-difluoro-4-iodopyridine step 2:

under nitrogen protection, at -78°c, add n-butyllithium (6.5 ml, 10.4 mmol, 1.6 m hexane solution) dropwise to 50 ml of diisopropylamine (1.5 ml, 4.8 mmol). of thf (5 ml) solution. after 20 minutes, a solution of 3-iodo-2,6-difluoropyridine (2.46 g, 10.4 mmol) in thf (12 ml) was added dropwise to the mixture via cannula. after maintaining the reaction at -78°c for 10 hours, thf (5 ml) and h₂o (0.51 g, 28 mmol) were added, and the mixture was warmed to room temperature within 1 hour. the mixture was washed with 10% na₂so₃ aqueous solution (10 ml) and extracted with ethyl acetate (150 ml). the organic extracts were dried (na₂so₄), concentrated in vacuo and the residue purified by chromatography (with 5:95 ethyl acetate/petroleum ether; rf = 0.6 elution), 2,6-difluoro-4-iodopyridine (1.72g, 70%) was obtained as colorless crystals, yield (1.72g, 70%), melting point 80-82°c.

references

[1] cheng d , croft l , abdi m , et al. synthetic entries to substituted bicyclic pyridones[j]. organic letters, 2007, 9(25):5175-5178.