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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Reaction Steps

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 (11.0 g, 28.3 mmol) in THF (700 mL) at −78° C. The mixture was stirred for 1 h, and ZnCl2 (0.71M in THF, 78.6 mL, 56.5 mmol) was added. This sol. was allowed to warm up to rt. A sol. of 4-trifluoromethanesulfonyloxy-5,6-dihydro-2H-pyridine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester (WO 2004/002957; 13.0 g, 34.5 mmol) in THF (30 mL) and Pd(PPh3)4 (814 mg, 0.704 mmol) were added. The mixture was stirred for 30 min at rt. Aq. sat. NH4Cl was added, and the mixture was extracted with EtOAc (2×). The combined org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the crude by FC (EtOAc/heptane 1:9→1:1) yielded the title compound (10.7 g, 70%). LC-MS: tR=1.16 min; ES+: 537.33.

Provenance & Evidence