[CH3:1][C@H:2]1[O:7][C@@H:6]([CH3:8])[CH2:5][NH:4][CH2:3]1.Cl[C:10]1[CH:15]=[C:14]([Cl:16])[CH:13]=[CH:12][N:11]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[Cl:16][C:14]1[CH:13]=[CH:12][N:11]=[C:10]([N:4]2[CH2:5][C@H:6]([CH3:8])[O:7][C@H:2]([CH3:1])[CH2:3]2)[CH:15]=1cis-2,6-Dimethylmorpholine (2.029 g, 17.62 mmol) was added to a suspension of 2,4-dichloropyridine (2.37 g, 16.01 mmol) and potassium carbonate (6.64 g, 48.0 mmol) in anhydrous acetonitrile (120 mL). After addition, the reaction mixture was stirred at 100° C. overnight. Crude LC/MS showed starting material and desired product so cis-2,6-dimethylmorpholine (0.500 equivalents) was added to the reaction mixture and then stirred and heated at 100° C. overnight. Crude LC/MS showed starting material and desired product so cis-2,6-dimethylmorpholine (0.500 equivalents) was added to the reaction mixture and then stirred and heated at 100° C. overnight. Crude LC/MS showed starting material and desired product so cis-2,6-dimethylmorpholine (0.500 equivalents) was added to the reaction mixture and then stirred and heated at 100° C. overnight. Crude LCMS showed desired product can be seen and no starting material left, so the reaction mixture was diluted with ethyl acetate (100 mL) and water (50 mL). The organic layer was separated and the aqueous layer was extracted with ethyl acetate (2×100 mL). The combined organic layer was dried (sodium sulfate), filtered and concentrated under reduced pressure. The residue was dissolved in dichloromethane (˜10 ml) and purified on silica by a Biotage SP4 chromatographic system (40+M cartridge, eluted with 0-100% ethyl acetate in isohexanes).
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