Sodium Carbonate → HCID 89649316, compound

Participants

Reaction Steps

5-Ethoxy-2-fluorophenylboronic acid (129.98 mg, 0.7100 mmol) and sodium carbonate (213.96 mg, 2.02 mmol) were added to a solution of (5S)-2-(4-bromo-2-pyridyl)-7-(2-trimethylsilylethoxymethyl)-1,7-diazaspiro[4.4]non-1-en-6-one (which may be prepared as described in Description 47) (295 mg, 0.6700 mmol) in monoglyme (6 mL) and water (1.8 mL) under N2 at ambient temp. The mixture was degassed by bubbling N2 through it for 10 mins. Bis(triphenylphosphine)palladium (II) dichloride (23.62 mg, 0.0300 mmol) was then added and the stirred mixture was refluxed under N2 for 2.25 h. The reaction was cooled, diluted with DCM (40 ml) and the solution washed with water (40 ml), dried (MgSO4) and evaporated to a dark brown oil, which was dried at RT under vacuum for 2 hours. This was purified by SiO2 column chromatography: the oil was dissolved in DCM (3 ml) and the solution was applied to a 10 g cartridge which was then eluted on a Biotage SP4 system with a gradient of EtOAc/iso-hexane (20-100%). Relevant fractions were pooled and evaporated to a light brown oil, dried at RT under vacuum for 16 hours to afford (S)-2-[4-(5-ethoxy-2-fluoro-phenyl)-pyridin-2-yl]-7-(2-trimethylsilanyl-ethoxymethyl)-1,7-diaza-spiro[4.5]dec-1-en-6-one (D48) 274 mg;

Provenance & Evidence