Ammonium Chloride → 6-[2-(2,6-Dichloro-4-methyl-phenoxy)-ethoxy]-5',6'-dihydro-2'H-[3,4']bipyridinyl-1',3'-dicarboxylic acid 1'-tert-butyl ester 3'-methyl ester

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BuLi (1.6M in hexane, 39.3 mL, 45.2 mmol) was added to a sol. of 5-bromo-2-[2-(2,6-dichloro-4-methyl-phenoxy)-ethoxy]-pyridine (13.0 g, 34.5 mmol) in THF (700 mL) at −78° C. The mixture was stirred for 1 h at −78° C., and ZnCl2 (0.72M in THF, 78.6 mL, 56.5 mmol) was added. The mixture was allowed to warm up to rt. 4-Trifluoromethanesulfonyloxy-5,6-dihydro-2H-pyridine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester (WO 2004/002957, 11.0 g, 28.3 mmol) and Pd(PPh3)4 (813 mg, 0.704 mmol) were added. The mixture was stirred for 30 min at 70° C., then overnight at rt. Aq. sat. NH4Cl was added, and the mixture was extracted with EtOAc (2×). The org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the crude by FC (heptane/EtOAc 9:1→5:5) yielded the title compound (10.7 g, 70%). LC-MS: tR=1.16 min; ES+: 537.33.

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