5-Bromo-2-iodopyridine → Methyl 1-(4-(2-(5-bromopyridin-2-yl)ethynyl)-3-fluorobenzyl)azetidine-3-carboxylate

Participants

Reaction Conditions

Reaction Steps

A solution of 5-bromo-2-iodopyridine (800 mg, 2818 μmol), methyl 1-(4-ethynyl-3-fluorobenzyl)azetidine-3-carboxylate (704 mg, 2846 μmol), and copper(I) iodide (21.5 mg, 113 μmol) in triethylamine (9.4 mL) was sparged with argon (30 sec), and PdCl2(PPh3)2 (79.1 mg, 113 μmol) was then added in one portion at 25° C. The reaction mixture was cooled to 0° C. and stirred for 40 min, and then allowed to stir at 25° C. for 1.5 h. The mixture was subsequently diluted with EtOAc (120 mL) and sequentially washed with water (4×30 mL) and brine (30 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. Chromatographic purification of the residue (silica gel, 0-100% EtOAc/Hexanes) furnished methyl 1-(4-(2-(5-bromopyridin-2-yl)ethynyl)-3-fluorobenzyl)azetidine-3-carboxylate as a light yellow oil. MS (ESI) m/z: Calculated: 402.0/404.0; Observed: 402.8/404.8 (M++1).

Provenance & Evidence