Synthesis conducted in flow using a FlowSyn (Uniqsis) flow system equipped with a home-made copper coil reactor, a standard T-piece mixer and 250 psi back-pressure regulator: A stream of a solution containing (−)-3-(4-ethynyl-phenyl)-1-(2-methyl-pyridin-4-yl)-3-o-tolyl-propan-1-one (150 mg in 5 mL, c=0.088 mol/L; example 287, step 2) and iodomethane (125 mg in 5 mL, c=0.177 mol/L) in ethyl acetate was combined with a second stream of sodium azide (58 mg in 5 mL, c=0.177 mol/L) in water and directed through a copper coil (volume=21 mL) at 150° C. Both channels were running at a flow rate of 0.4 mL/min, which equals to a residence time of 26 min. The product stream was collected in a 25% solution of ammonium hydroxide and extracted with ethyl acetate (3×50 mL). The combined organic phases were dried over sodium sulfate and the crude reaction product purified by silica gel chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane/ethyl acetate (1:1 to 2:1) to provide the title compound as a colorless solid. MS (ESI+): m/z=397.3 ([M+H]+).
