Sodium Carbonate → (rac.)-(1R*,5S*)-3-(6-Bromo-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 Steps

6-Bromopyridine-3-boronic acid (5.00 g, 24.8 mmol), Pd(OAc)2 (278 mg, 1.24 mmol) and PPh3 (650 mg, 2.48 mmol) were suspended in EtOH (67 mL). A sol. of Na2CO3 (3.15 g, 29.7 mmol) in water (25.3 mL) was added. A sol. of compound A1 (10.3 g, 24.8 mmol) in THF (25 mL) was added, and the mixture was heated to reflux for 4 h. 6-Bromopyridine-3-boronic acid (5.00 g, 24.8 mmol) was added again, and 1 h later Pd(OAc)2 (278 mg, 1.24 mmol) and PPh3 (650 mg, 2.48 mmol) and Na2CO3 (3.15 g, 29.7 mmol) were added. The mixture was stirred at reflux for 1 h, and was allowed to cool to rt. The solvents were removed under reduced pressure. EtOAc was added, and the mixture was washed with aq. sat. NaHCO3 (2×), with aq. sat. NH4Cl, and with brine. The org. layer was dried over Na2SO4, filtered, and the solvents were removed under reduced pressure. Purification of the crude by FC (EtOAc/heptane 20:80) yielded the title compound (4.24 g, 40%). LC-MS: tR=1.01 min, ES+: 423.19.

Provenance & Evidence