Sodium Hydroxide → 7-Methoxy-9-nitro-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Participants

Reaction Conditions

Reaction Steps

7-Methoxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (750 mg/4.2 mmol) was dissolved in a mixture of dry acetonitrile (3 mL) and trifluoroacetic anhydride (3 mL) and cooled to 0° C. (ice bath). The trifluoroacetyl amide of the benzazepine forms immediately (observed by HPLC). Potassium nitrate (450 mg/4.2 mmol) was added in one portion and the mixture allowed to warm to room temperature. After one hour the reaction was complete (HPLC); 33% sodium hydroxide (1 mL) was added via pipette (exotherm) and the mixture stirred for an additional two hours (to hydrolyze the TFA amide). The resulting mixture was partitioned between water (20 mL) and methylene chloride (20 mL). The aqueous layer was extracted with an additional portion of methylene chloride (20 mL) and the combined organics were dried over magnesium sulfate, filtered and concentrated to afford a 1.7:1 ratio of 7-Methoxy-8-nitro-2,3,4,5-tetrahydro-1H-benzo[d]azepine and 7-Methoxy-9-nitro-2,3,4,5-tetrahydro-1H-benzo[d]azepine as a yellow oil (770 mg/82%). The material was used without further purification. 1H NMR (400 MHz, CDCl3) major isomer: δ 7.66 (s, 1H), 6.82 (s 1H); minor isomer: 7.14 (d, J=8.3 Hz, 1H), 6.76 (d, J=8.3 Hz, 1H).

Provenance & Evidence