反应详情

To a solution of 6-Methoxy-1-methyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-one (INT-1) (538 mg, 2.62 mmol) in acetonitrile brought to 0° C. in an ice bath was added 1.8 mL TFAA (2.7 g, 13.1 mmol), followed by KNO3 (320 mg, 3.14 mmol). After approximately 5 minutes, the reaction was allowed to warm to room temperature. Conversion of starting material to product was monitored by LC/MS. Upon completion, the reaction was cooled to 0° C. in an ice bath and quenched with sat. NaHCO3 (aq), 1N NaOH (aq), and ice until pH ˜9-10 was achieved. The aqueous mixture was extracted 3× with EtOAc and the organic layers were washed with brine, dried with MgSO4, and concentrated to give 6-Methoxy-1-methyl-7-nitro-1,3,4,5-tetrahydro-benzo[b]azepin-2-one (INT-2) as an orange solid (530 mg, 82%). By NMR, the product showed a 4:1 mixture of nitration products, 80% of which was the desired product. By TLC, the products appeared inseparable, so the material was taken on for reduction crude. Data for Major Isomer: 1H-NMR (CDCl3) δ 7.83 (d, J=8.8 Hz, 1H), 7.04 (d, J=8.8 Hz, 1H), 3.94 (s, 3H), 3.37 (s, 3H), 2.87 (br m, 2H), 2.36 (t, J=7.1 Hz, 2H), 2.24 (m, 2H); LC/MS (ESI-pos) m/z 251.03 (M+H).

1. temperatureUpon completion, the reaction was cooled to 0° C. in an ice bath
2. customquenched with sat. NaHCO3 (aq), 1N NaOH (aq), and ice until pH ˜9-10
3. extractionThe aqueous mixture was extracted 3× with EtOAc
4. washthe organic layers were washed with brine
5. dry with materialdried with MgSO4
6. concentrationconcentrated