Acetone → HCID 112757186, compound

Participants

Reaction Conditions

Reaction Steps

3-Amino-5-bromopyridine (Aldrich, 5.0 g, 28.9 mmol), acetone (6.37 ml, 87 mmol), Zinc chloride (0.5 M in THF) (11.56 ml, 5.78 mmol) were combined in acetonitrile (150 ml) and cooled to 0° C. The reaction was stirred for 10 min and trimethylsilylcyanide (10.46 ml, 78 mmol) was added dropwise. The reaction was heated to 85° C. in an oil bath with a reflux condensor. The reaction was monitored by LCMS and at 2 hrs the reaction was 80% complete. The reaction was cooled to room temperature and additional acetone (1.2 mL) and trimethylsilylcyanide (3 mL) added. The reaction was allowed to stir 18 hrs at 85° C. The reaction mixture was concentrated to reduce the volume by 50% and mixture poured into brine (100 mL). The pH was adjusted to 7.5 with aq. NaHCO3 and the product extracted with ethyl acetate (2×100 mL). The combined organic extracts were washed with brine, dried over Na2SO4, and resulting solution filtered thru a pad of silica. The filtrate was concentrated and the residue purified by silica gel chromatography, Biotage SNAP 100 g, eluting with EtOAc/isohexane (0-100%) to give 6.42 g, 93% yield of the desired product as an off-white solid, I-4a.

Provenance & Evidence