5-Bromo-2-(2-(2,6-dichloro-4-methylphenoxy)ethoxy)pyridine → (rac.)-(1R*,5S*)-3-{6-[2-(2,6-Dichloro-4-methyl-phenoxy)-ethoxy]-pyridin-3-yl}-8-aza-bicyclo[3.2.1]oct-2-ene-2,8-dicarboxylic Acid 8-tert-butyl Ester 2-methyl Ester

Participants

Reaction Conditions

Reaction Steps

BuLi (1.6 M in hexane, 12.0 mL, 19.2 mmol) was added to the sol. of 5-bromo-2-[2-(2,6-dichloro-4-methyl-phenoxy)-ethoxy]-pyridine (5.45 g, 14.4 mmol) in THF (120 mL) at −78° C. The mixture was stirred at −78° C. for 60 min, and ZnCl2 (1M in THF, 28.9 mL, 28.9 mmol) was added. The mixture was allowed to warm up to rt, and compound A1 (4.00 g, 9.63 mmol) in dry THF (50 mL) and Pd(PPh3)4 (277 mg, 0.240 mmol) in THF (2 mL) were added. The mixture was heated to 70° C. for 1 h, and was quenched with aq. sat. NH4Cl (70 mL). The mixture was extracted with EtOAc (3×). The combined org. layers were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of crude by FC(CH2Cl2/MeOH 99:1→98:2→97:3→96:4→95:5) yielded the title compound (4.25 g, 78%). LC-MS: tR=1.16 min; ES+: 563.11.

Provenance & Evidence