Pyridine, 2-[2-(1,1-dimethylethyl)phenoxy]-3-iodo- synthesis

Yield:861674-06-8 56%

Reaction Conditions:

Stage #1: 2-(2-(tert-butyl)phenoxy)pyridin-3-aminewith hydrogenchloride;sodium nitrite in water at 0; for 0.25 h;
Stage #2: with potassium iodide in water at 0 - 60; for 1.5 h;

Steps:

141a

141a 2- (2-telt-butylphenoxy)-3-iodopyridine [00371J A solution of sodium nitrite (157 mg, 2.28 mmol) in water (1 mL) was added to a mixture of 2- (2-tert-butylphenoxy)-3-aminopyridine (prepared above according to lb) (500 mg, 2.07 mmol) in (1: 1) conc. HCl : water (14 mL) at 0°C. The mixture was stirred at 0°C for 15 min and a solution of potassium iodide (1.0 g, 6.22 mmol) in water (2 mL) was added. The mixture was stirred at 60°C for 1.5 h and allowed to cool down to rt. A solution of sodium bisulfite was added and the mixture was extracted with ethyl acetate (3 x 50 mL). The combined organic layers were dried (anhydrous sodium sulfate), filtered and evaporated. The residue was purified by flash-chromatography (dichloromethane : hexanes/20: 1. 00) to afford 394 mg (56%) of 2- (2-tert-butylphenoxy)-3-iodopyridine. (M+H) + = 354.

References:

WO2005/70920,2005,A1 Location in patent:Page/Page column 1116