Hydrochloric Acid → (S)-4-Chloro-1-methoxy-2-nitro-6,7-dihydro-5H-benzocyclohepten-7-ylamine

Participants

Reaction Conditions

Reaction Steps

A mixture of the crude N—((S)-4-Chloro-9-(R,S)-hydroxy-1-methoxy-2-nitro-6,7,8,9-tetrahydro-5H-benzocyclohepten-7-yl)-acetamide and 6 M of Hydrogen Chloride in Water (15 mL) were warmed to 95° C. for 3 days. The reaction mixture was then cooled and treated slowly with 30% aqueous NaOH. When the pH proved >10, the reaction mixture was extracted with Et2O (3×). The organic phases were combined, dried over Na2SO4, filtered and concentrated under reduced pressure. The resulting residue was dissolved in CH2Cl2, dried over Na2SO4, filtered, and then chromatographed on a normal phase column eluting with a gradient of 100% CH2Cl2 to 5:1 CH2Cl2:MeOH to give 42 mg (50% over two steps) of (S)-4-Chloro-1-methoxy-2-nitro-6,7-dihydro-5H-benzocyclohepten-7-ylamine as an oil, which was used for subsequent steps without further manipulation. 1H NMR (400 MHz, CDCl3) δ 7.79 (s, 1H), 6.68 (d, J=12.37 Hz, 1H), 6.23-6.19 (dd, J=4.29 Hz, 11.98 Hz, 1H), 3.89 (s, 3H), 3.56 (m, 1H), 3.15 (m, 1H), 2.74-2.66 (m, 1H), 2.28 (m, 1H), 2.01 (m, 1H); MS (m/e) weak parent at 269 (M+H).

Provenance & Evidence