Sodium Carbonate → (3R,4S)-1-Pyridin-3-yl-4-[4'-(2-pyrrolidin-1-yl-ethoxy)biphenyl-4-yloxy]pentan-3-ol

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 (0.190 g, Example 33), 1-[2-(4-bromophenoxy)ethyl]pyrrolidine (0.27 g), 2M aqueous sodium carbonate (0.75 ml) and tetrakis(triphenylphosphine)palladium (0) (0.025 g) in ethanol (2 ml). The reaction mixture was heated at 90° C. for 4 hours. After cooling, the solution was concentrated under reduced pressure, taken up in ethanol and concentrated again (twice). The residue was triturated with acetone and then filtered through silica gel. The filtrate was concentrated under reduced pressure, dissolved in dichloromethane, filtered and purified by normal-phase HPLC eluting with a gradient of 0-25% ethanol in dichloromethane to give an oil which crystallised under high vacuum over 24 hours. Trituration with diethyl ether resulted in isolation of the title compound as a foam (0.194 g).

Provenance & Evidence