Nitrogen → (rac.)-(1R*,5S*)-7-{6-[3-(2-Chloro-3,6-difluoro-phenyl)-isoxazol-5-ylmethoxy]-pyridin-3-yl}-3,9-diaza-bicyclo[3.3.1]non-6-ene-3,6,9-tricarboxylic Acid 3,9-di-tert-butyl Ester 6-methyl Ester

Participants

Reaction Conditions

Reaction Steps

(rac.)-(1R*,5S*)-7-Trifluoromethanesulfonyloxy-3,9-diaza-bicyclo[3.3.1]non-6-ene-3,6,9-tricarboxylic acid 3,9-di-tert-butyl ester 6-methyl ester (WO 2006/021402, 4.72 g, 8.90 mmol) and 2-[3-(2-chloro-3,6-difluoro-phenyl)-isoxazol-5-ylmethoxy]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridine (5.77 g crude, about 13.4 mmol) were dissolved in a mixture of DME (59.3 mL) and aq. 2M Na2CO3 (44.5 mL). The mixture was degassed with N2, and Pd(PPh3)4 (514 mg, 0.445 mmol) was added. The mixture was heated rapidly to 80° C., and was stirred at this temperature for 1 h. The mixture was diluted with EtOAc (100 mL), and washed with water (100 mL). The org. layer was dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the crude by FC (EtOAc 100%→EtOAc/MeOH 95:5) yielded the title compound (4.56 g, 73%). LC-MS: tR=1.15 min, ES+: 703.25.

Provenance & Evidence