4- Iodo-2-fluoropyridine

Iodo-2-fluoropyridine (15.52 g, 69.60 mmol) was dissolved in dry THE (150 mL) and cooled to -70 °C. Then n-BuLi (73.08 mmol, typically a solution in hexanes) was added, and the reaction was stirred at -70 °C for 20 min. Subsequently, dry zinc chloride (10.44 g, 76.61 mmol) was added as a solution in dry THE (60 mL) while keeping the temperature below -60 °C. (Use an internal thermometer.) The reaction mixture was then wanned to room temperature whereupon tetrakis (triphenylphosphine)palla-dium (0.40 g, 0.35 mmol) and 2,4-dichloropyrimidine (7.26 g, 48.73 mmol) in THE (100 mL) were added, and the reaction mixture was refluxed until complete conversion. The reaction mixture was poured into a 10% aqueous EDTA solution and extracted with CH2CI2. The crude material was purified by flash chromatography eluting with petro-leuni ether EtOAc (10 1) to deliver 9.17 g (90%) of the pyrimidine as beige crystals. 

Radiolabeled 4-[ F]fluoropyridine can be synthesized by no-carrier-added nucleophilic aromatic substitution with K[ F]F-K222- In another instance, the nucleophilic substitution reaction was also employed for the synthesis of steroids-containing 4-fluoropyridine motif, and for the synthesis of 4-fluoropyridines annulated with pyrrole (azoindoles).Substantial difference in the reactivity of the pyridinium ring toward nucleophilic substitution in 5-iodo-2,4-difluorpyridine was effectively used for the preparation of 4-fluoropyridines 93 and 94 using difluoropyridine 92 as starting material (Scheme 6.31). 

Reaction of 2-chloro- or 2-iodo-pyridine with potassamide in liquid ammonia , or of 2-fluoropyridine with lithium piperidide in ether results in direct substitution without pyridyne intermediates. The reaction of 3-fluoropyridine with potassamide in liquid ammonia at —33° takes a surprising course . Evidently the base abstracts a proton from the 4-... 

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