Sodium Carbonate → (1S, 2R)-2-[4'(2-Hydroxy-1-methyl-4-pyridin-3-ylbutoxy)biphenyl-3-yl]-N-methylacetamide

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Reaction Steps

A solution of (1S,2R)-4-[2-(tert-butyldimethylsilanyloxy)-1-methyl-4-pyridin-3-ylbutoxy]benzeneboronic acid (0.20 g, Example 11), 2-(3-bromophenyl)-N-methyl -acetamide (0.21 g, Example 12a)), 2M aqueous sodium carbonate (0.57 ml) and tetrakis(triphenylphosphine)palladium (0) (0.1 g) in toluene (5 ml) and ethanol (2 ml) was heated at 100° C. for 4 hours. After cooling, the solution was concentrated under reduced pressure. Concentrated hydrochloric acid (1 ml) was added to a solution of the residue in methanol (5 ml). The suspension was stirred at room temperature for 18 hours. The mixture was concentrated under reduced pressure and the residue partitioned between ether and water. The aqueous layer was neutralised and extracted with dichloromethane (2×50 ml). The combined extracts were dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by normal-phase HPLC eluting with a gradient of 0-25% ethanol in dichloromethane to give the title compound as an oil (0.15 g).

Provenance & Evidence