Triethylamine → (S)-2-(1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl)-7-nitroisoindolin-1-one

Participants

Reaction Steps

A solution of 2-bromomethyl-6-nitro-benzoic acid methyl ester (4.0 g, 14.6 mmol), (1S)-1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethylamine (4.0 g, 14.6 mmol) and triethylamine (4.4 mL, 31.6 mmol) in DMF (40 mL) was heated at 80° C.-90° C. for 1 day. The solvent was removed in vacuo to give an oil. The oil was extracted with ethyl acetate (150 mL) and HCl (2N, 50 mL). The organic layer was washed with HCl (2N, 2×50 mL), water (2×50 mL), brine (2×50 mL) and dried over MgSO4. The solvent was removed in vacuo to give a yellow oil. The oil was slurried in ether (50 mL) to give a suspension. The suspension was filtered and washed with ether to give 2-[(1S)-1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-7-nitro-2,3-dihydro-isoindol-1-one as a yellow solid (3.43 g, 54% yield): 1H NMR (CDCl3) δ 1.5 (t, J=7 Hz, 3H, CH3), 2.99 (s, 3H, CH3), 3.69 (dd, J=5, 15 Hz, 1H, CHH), 3.86 (s, 3H, CH3), 4.07 (q, J=7 Hz, 2H, CH2), 4.27 (dd, J=11, 15 Hz, 1H, CHH), 4.30 (d, J=17 Hz, 1H, NCHH), 4.54 (d, J=17 Hz, 1H, NCHH), 5.70 (dd, J=5, 10 Hz, 1H, NCH), 6.85 (d, J=8 Hz, 1H, Ar), 6.94-7.00 (m, 2H, Ar), 7.58-7.76 (m, 3H, Ar).

Provenance & Evidence