COC(=O)Cc1cc(Br)ccn1.Cl.FC1(F)CNC1>CC(=O)O.CC(=O)O.CN(C)C=O.O=C([O-])[O-].[Cs+].[Cs+].[Pd].c1ccc(P(c2ccccc2)c2ccc3ccccc3c2-c2c(P(c3ccccc3)c3ccccc3)ccc3ccccc23)cc1>COC(=O)Cc1cc(N2CC(F)(F)C2)ccn1palladium acetate (1.561 mg, 6.95 µmol) and BINAP (2.71 mg, 4.35 µmol) were added to methyl 2-(4-bromopyridin-2-yl)acetate (100 mg, 0.43 mmol), 3,3 difluoroazetidine hydrochloride (61.9 mg, 0.48 mmol) and cesium carbonate (425 mg, 1.30 mmol) in DMF (5 mL) at 21°C under nitrogen. The resulting mixture was stirred at 120 °C for 2.5 hours. - lcms looks ok. Cooled to room temp.The reaction mixture was diluted with EtOAc (150 mL), and washed sequentially with water (75 mL), water (75 mL). The organic layer was dried over Na2SO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 30 to 50% EtOAc in heptane. Pure fractions were evaporated to dryness - 200mg yellow oil. Contained Pd impurities. The crude product was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 1M NH3/MeOH and pure fractions were evaporated to dryness to afford methyl 2-(4-(3,3-difluoroazetidin-1-yl)pyridin-2-yl)acetate (42.0 mg, 39.9 %) as a yellow gum. maybe better to avoid aq w/u and just purify by SCX column.
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