1-Bromo-2,3-difluorobenzene → (6S,9R)-6-(2,3-Difluorophenyl)-6,7,8,9-tetrahydro-9-[[tris(1-methylethyl)silyl]oxy]-5H-cyclohepta[b]pyridin-5-one

Participants

Reaction Conditions

Reaction Steps

See Fox, J. M.; Huang, X.; Chieffi, A.; Buchwald, S. L. J. Am. Chem. Soc. 2000, 122, 1360-1370. In an oven-dried 1 L flask was Sodium tert-butoxide (13.19 g, 137 mmol), PALLADIUM(II) ACETATE (0.948 g, 4.22 mmol), and 2-(Dicyclohexylphosphino)-2′-methylbiphenyl (1.539 g, 4.22 mmol) weighed in a nitrogen bag. (R)-9-(triisopropylsilyloxy)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-5-one (35.21 g, 106 mmol), Toluene (106 mL) (degassed in the original bottle by nitrogen gas), and 1-bromo-2,3-difluorobenzene (14.18 mL, 127 mmol) were added under nitrogen. The flask stirred at 80° C. in a pre-heated oil bath for 20 h. Volatiles were stripped off and the residue was partitioned between EtOAc (400 ml) and water (400 ml). The layers were separated. The aqueous layer was extracted with EtOAc (50 ml). The combined organic layer was washed with brine, dried and concentrated to a dark oil. It was passed through a plug of silica gel (loaded with CH2Cl2 and eluted with EtOAc/hexane up to 30% EtOAc). The crude product was obtained as a dark red oil (86% mass recovery). 1H NMR showed approximately 6/1 ratio of the desired trans isomer to the cis isomer. MS (ESI)[M+H+]=446.21.

Provenance & Evidence