2,7-Dibromo-9-fluorenone → 3-(7-Bromo-9-oxo-9H-fluoren-2-yl)-(1R,5R)-3,6-diazabicyclo[3.2.0]heptane-6-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

A mixture of 3,6-diazabicyclo[3.2.0]heptane-6-carboxylic acid tert-butyl ester (600 mg, 3.0 mmol; prepared according to patent WO2001081347), 2,7-dibromo-fluoren-9-one (1.3 g, 4 mmol; Aldrich), sodium tert-butoxide (400 mg, 4.2 mmol; Aldrich), tris(dibenzylideneacetone)dipalladium (Pd2(dba)3; 160 mg, 0.17 mmol; Alfa) and racemic 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP; 330 mg, 0.53 mmol; Strem) in dry toluene (30 mL) was warmed to 85° C. and stirred under nitrogen atmosphere for 3 h. The reaction mixture was concentrated under vacuum and purified by flash chromatography (80 g silica gel, 40:60 hexanes-EtOAc) to afford the title compound (800 mg, 1.76 mmol; 55% yield): 1H NMR (300 MHz, CD3OD) δ ppm 7.56-7.61 (2H, m), 7.47 (1H, d, J=8 Hz), 7.38 (1H, d, J=8 Hz), 7.06 (1H, d, J=3 Hz), 6.92 (1H, dd, J=8, 3 Hz), 4.60-4.67 (1H, m), 3.91-4.16 (2H, m), 3.73-3.86 (1H, m), 3.55-3.66 (1H, m), 3.41-3.51 (1H, m), 2.90-3.27 (3H, m), 1.36-1.55 (9H, s); MS (DCl/NH3): m/z 455 (M+1)+, 457 (M+3)+.

Provenance & Evidence