Trifluoroacetic anhydride → (1S,2R)-2,2,2-Trifluoro-N-[4'-(2-hydroxy-1-methyl-4-pyridin-3-yl-butoxy)-biphenyl-3-yl]-N-methylacetamide

Participants

Reaction Conditions

Reaction Steps

Prepared according to the method described in Example 12b) from (1S,2R)-4-(2-hydroxy-1-methyl-4-pyridin-3-ylbutoxy)benzeneboronic acid (0.150 g, Example 33), N-(3-bromo-phenyl)-2,2,2-trifluoro-N-methylacetamide (0.282 g), 2M aqueous sodium carbonate (0.50 ml) and tetrakis(triphenylphosphine)palladium (0) (0.020 g) in ethanol (3 ml) with heating at 90° C. for 2 hours. After work up, the residue was purified by normal-phase HPLC eluting with a gradient of 0-25% ethanol in dichloromethane. The product obtained was dissolved in dichloromethane (3 ml), and cooled to 0° C. Trifluoroacetic anhydride (0.09 ml) was added dropwise, the reaction mixture stirred for 1 hour at room temperature, before concentrating under reduced pressure. Methanol (10 ml) and water (10 ml) were added and the resulting mixture was stirred for 30 minutes at room temperature. The product was extracted with ethyl acetate, and the combined extracts were dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give the title compound as an oil (0.148 g).

Provenance & Evidence