3-IODO-4-METHOXY-PYRIDINE synthesis

Yield: 89%

Reaction Conditions:

Stage #1:4-methoxypyridine with 2,2,6,6-tetramethyl-piperidine;n-butyllithium;zinc dichloro(N,N,N′,N′-tetramethylethylenediamine) in tetrahydrofuran;hexane at 20; for 2 h;Inert atmosphere;
Stage #2: with iodine in tetrahydrofuran;hexane at 20;Inert atmosphere;regioselective reaction;Concentration;

Steps:

4.2. General procedure 1
General procedure: To a stirred, cooled (0 C) solution of 2,2,6,6-tetramethylpiperidine (0.25 mL, 1.5 mmol) in THF (2-3 mL) were successively added BuLi (about 1.6 M hexanes solution, 1.5 mmol) and, 5 min later, ZnCl2TMEDA[51] (0.13 g, 0.50 mmol). The mixture was stirred for 15 min at 0 C before introduction of the substrate (1.0 mmol) at 0-10 C. After 2 h at room temperature, a solution of I2 (0.38 g, 1.5 mmol) in THF (4 mL) was added. The mixture was stirred overnight before addition of an aqueous saturated solutionof Na2S2O3 (4 mL) and extraction with AcOEt (320 mL). The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure. Purification by chromatographyon silica gel (the eluent is given in the product description) led to the compounds described below.

References:

Hedidi, Madani;Bentabed-Ababsa, Ghenia;Derdour, Aïcha;Halauko, Yury S.;Ivashkevich, Oleg A.;Matulis, Vadim E.;Chevallier, Floris;Roisnel, Thierry;Dorcet, Vincent;Mongin, Florence [Tetrahedron,2016,vol. 72,# 17,p. 2196 - 2205]