Cesium carbonate → 1-Azetidinecarboxylic acid, 3-(6-bromo-2-methyl-1H-benzimidazol-1-yl)-, 1,1-dimethylethyl ester

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Reaction Steps

A flask was charged with 4-bromo-2-fluoro-1-nitrobenzene (529 mg, 2.41 mmol), Cs2CO3 (2.45 g, 7.52 mmol), and diluted with DMF (6 mL). To this was added tert-butyl 3-aminoazetidine-1-carboxylate (0.75 mL, 4.78 mmol) at room temperature and the reaction mixture was allowed to stir for 16 hours. The mixture was diluted with EtOAc and H2O and the layers were separated. The aqueous layer was extracted with EtOAc and the combined organic extracts were dried over Na2SO4, filtered through a small pad of silica gel eluting with 30% EtOAc/Hex, and concentrated in vacuo to afford a crude residue. The flask containing the crude residue was charged 5 wt % Pt/C (140 mg) and then diluted with 2:1 EtOH/EtOAc (30 mL). The flask was evacuated then backfilled with H2 (3 cycles) and stirred under a hydrogen atmosphere for 20 minutes, at which time, the flask was purged with N2, filtered through a pad of Celite, and concentrated in vacuo to provide a crude residue. The crude residue was taken up in AcOH (10 mL) and MeC(OEt)3 (1 mL) was added at room temperature, stirred for 15 minutes, and then the solution was concentrated in vacuo. The crude residue was purified by silica gel column chromatography (30-70% EtOAc/Hex gradient) to afford the desired product. LCMS-ESI+: calc'd C16H21BrN3O2: 366.1 (M+H+); Found: 366.1 (M+H+).

Provenance & Evidence