反应详情

温度

95 °C

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).

1. temperatureThe reaction mixture was then cooled
2. extractionthe reaction mixture was extracted with Et2O (3×)
3. dry with materialdried over Na2SO4
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. dissolutionThe resulting residue was dissolved in CH2Cl2
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. customchromatographed on a normal phase column
10. washeluting with a gradient of 100% CH2Cl2 to 5:1 CH2Cl2