Ammonium formate → Methyl 3-(3,5-dimethoxyphenyl)-2-[4-[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]phenyl]prop-2-enoate

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Reaction Conditions

Reaction Steps

Compound 10 (20 g, 38.6 mmol), ammonium formate (150 g, 2.38 mol), 10% Pt/C (dry, 4 g) and acetic acid (660 mL) were combined into a round bottom flask equipped with reflux condenser, thermometer and mechanical stirrer. The reactor was evacuated and purged three times with nitrogen then, heated to a steady reflux (ca. 124° C.). Reaction was completed within 15 h and allowed to cool with stirring to ambient room temperature. After cooling, the mixture was filtered though a pad of Celite® (5 g) and the filter pad washed with fresh acetic acid (2×100 mL). The mother liquor and washes were combined and concentrated. The residue was then diluted with dichloromethane (400 mL), and the combined organics were extracted twice with water (400 mL) and 5% bicarbonate (400 mL). The organic portion was then dried and poured through silica gel (30 g) and washed with dichloromethane (2×100 mL). The washes were combined and concentrated. The residue was diluted with ethanol, allowed to cool to 60° C. and seed crystals were added. This slurry was stirred at 50° C. for about 30 min then allowed to cool to ambient room temperature to yield compound 11 (12.85 g, 64%) with an HPLC assay of 98.1%.

Provenance & Evidence