(R)-(+)-1-Boc-3-aminopyrrolidine → tert-butyl (3R)-3-[(2'-oxo-1'-{[5-(trifluoromethyl)furan-2-yl]methyl}-1',2'-dihydrospiro[1-benzofuran-3,3'-indol]-6-yl)amino]pyrrolidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 6-bromo-1′-{[5-(trifluoromethyl)furan-2-yl]methyl}spiro[1-benzofuran-3,3′-indol]-2′(1′H)-one (0.80 g, 1.73 mmol), (R)-1-Boc-3-aminopyrrolidine (0.48 g, 2.59 mmol) and (2-biphenyl)di-tert-butylphosphine (0.08 g, 0.28 mmol) in toluene (15 mL) was added palladium(II) acetate (0.09 g, 0.14 mmol) followed by the addition of sodium tert-butoxide (0.42 g, 4.3 mmol). The mixture was stirred at 100° C. for 18 h. The mixture was filtered through a pad of celite, and the filtrate was concentrated in vacuo. The residue was subjected to column chromatography (ethyl acetate/hexane; 1/2) to afford tert-butyl (3R)-3-[(2′-oxo-1′-{[5-(trifluoromethyl)furan-2-yl]methyl}-1′,2′-dihydrospiro[1-benzofuran-3,3′-indol]-6-yl)amino]pyrrolidine-1-carboxylate (0.47 g, 48%): 1H NMR (300 MHz, CDCl3) δ7.32-7.24 (m, 1H), 7.17 (d, J=7.4 Hz, 1H), 7.05 (dd, J=7.4 Hz, 1H), 6.95 (d, J=7.8 Hz, 1H), 6.76-6.69 (m, 1H), 6.45 (d, J=8.2 Hz, 1H), 6.36 (d, J=3.2 Hz, 1H), 6.19 (d, J=2.0 Hz, 1H), 6.02 (dd, J=8.2, 2.0 Hz, 1H), 5.05 (d, J=16.2 Hz, 1H), 4.95-4.81 (m, 2H), 4.65 (d, J=9.0 Hz, 1H), 4.00-3.90 (m, 1H), 3.88-3.76 (m, 1H), 3.73-3.57 (m, 1H), 3.52-3.34 (m, 2H), 3.30-3.11 (m, 1H), 2.23-2.06 (m, 1H), 1.96-1.77 (m, 1H), 1.45 (s, 9H); MS (ES+) m/z 570.2 (M+1).

Provenance & Evidence