Dimethylformamide → 4-(Isocyano(tosyl)methyl)-1-tosylpiperidine

Participants

Reaction Steps

NaH (0.92 g, 23.07 mmol, 60% dispersion in oil) was added to DMF (70 mL) in one portion at 0° C. Toluenesulphonylmethyl isocyanide (3.0 g, 15.38 mmol) in DMF (12 mL) was added dropwise over 5 minutes and the mixture was stirred while warming to r.t. for 20 minutes. 4-Bromo-1-tosylpiperidine (4.46 g, 18.4 mmol) in DMF (10 mL) was then added dropwise over 3 minutes and the resulting mixture was stirred at r.t. for 16 h. The mixture was then diluted with ethyl acetate (250 mL) and LiCl (1 M aqueous solution, 60 mL), and the separated organic layer was washed with water (60 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (20% EtOAc/hexane) to provide 4-(isocyano(tosyl)methyl)-1-tosylpiperidine as a white solid: 1H NMR (400 MHz, CDCl3) δ 7.79 (d, J=8.0 Hz, 2H), 7.61 (d, J=7.6 Hz, 2H), 7.38 (d, J=8.0 Hz, 2H), 7.32 (d, J=7.6 Hz, 2H), 4.34 (d, J=4.0 Hz, 1H), 3.87-3.84 (m, 2H), 2.44 (s, 3H), 2.43 (s, 3H), 2.30-2.10 (m, 2H), 2.10-2.0 (m, 1H), 2.0-1.70 (m, 4H); MS (ESI) 451.1 (M+H+H2O)+.

Provenance & Evidence