Dimethylformamide → Tert-butyl 2-(4-cyano-1-oxoisoindolin-2-yl)-4-carbamoylbutanoate

Participants

Reaction Conditions

Reaction Steps

A mixture of tert-butyl 2-(4-bromo-1-oxoisoindolin-2-yl)-4-carbamoylbutanoate (1.2 g, 3.02 mmol), zinc cyamide (0.21 g, 1.81 mmol), tris(dibenzylideneacetone)dipalladium (0.06 g, 0.06 mmol), 1,1′-bis(diphenylphosphino)ferrocene (0.067 g, 0.12 mmol) in deoxygenated DMF (15 mL) was heated to 120° C. under N2 for 6 hours. The mixture was cooled to room temperature and poured into EtOAc (100 mL) and sat. NaHCO3 (40 mL). The EtOAc solution was washed with water (2×40 mL), brine (40 mL), and dried (MgSO4). Solvent was removed and the residue was purified by chromatography (CH2Cl2: CH3OH 97.5:2.5) to afford tert-butyl 2-(4-cyano-1-oxoisoindolin-2-yl)-4-carbamoylbutanoate (0.77 g, 74%): 1H NMR (CDCl3) δ 8.07-8.03 (dd, J=0.7 and 7.4 Hz, 1H), 7.86-7.83 (dd, J=1.0 and 7.9 Hz, 1H), 7.61 (t, J=7.6 Hz, 1H), 5.91 (s, 1H), 5.68 (s, 1H), 5.03-4.98 (m, 1H), 4.85 (d, J=17.9 Hz, 1H), 4.62 (d, J=17.9 Hz, 1H), 2.48-2.41 (m, 4H), 1.46 (s, 9H); 13C NMR (CDCl3) δ 173.56, 169.21, 167.70, 145.23, 134.94, 133.11, 128.93, 128.21, 115,65, 107.86, 82.98, 63.68, 54.47, 46.55, 32.34, 27.95, 25.46.

Provenance & Evidence