反应详情

A suspension of 220 (410 mg, 1.02 mmol) in CH2Cl2 (15 mL) containing DMF (1 drop) was treated with oxalyl chloride (0.27 mL, 3.10 mmol) and stirred at room temperature for 30 min. The mixture was evaporated under reduced pressure and azeotroped dry with benzene. The resulting acid chloride was dissolved in acetone (5 mL) and treated at 0° C. with a solution of NaN3 (300 mg, 4.6 mmol) in water (1 mL). The mixture was shaken at room temperature for 1 min, and the precipitate was collected, dried, and stirred in toluene (15 mL) at reflux for 1.5 h. After addition of t-BuOH (1.0 mL, 10 mmol) the mixture was heated at reflux for 5 min then concentrated under reduced pressure. The residue was purified by chromatography, eluting with CH2Cl2, followed by crystallisation from CH2Cl2/hexane to give tert-butyl 1-(chloromethyl)-5-nitro-3-(trifluoroacetyl)-1,2-dihydro-3H-benzo[e]indole-7-carbamate (221) (347 mg, 72%) as an orange solid: mp 219-220° C.; 1H NMR [(CD3)2SO] δ 9.93 (s, 1H), 8.94 (s, 1H), 8.71 (d, J=1.9 Hz, 1H), 8.19 (d, J=9.2 Hz, 1H), 7.82 (dd, J=9.2, 2.0 Hz, 1H), 4.65-4.42 (m, 3H), 4.17 (dd, J=11.3, 2.8 Hz, 1H), 4.09 (dd, J=11.3, 5.2 Hz, 1H), 1.52 (s, 9H). Anal. (C20H19ClF3N3O5) C, H, N.

1. customThe mixture was evaporated under reduced pressure
2. customazeotroped
3. dry with materialdry with benzene
4. dissolutionThe resulting acid chloride was dissolved in acetone (5 mL)
5. stirringThe mixture was shaken at room temperature for 1 min
6. customthe precipitate was collected
7. customdried
8. stirringstirred in toluene (15 mL)
9. temperatureat reflux for 1.5 h
10. temperaturewas heated
11. temperatureat reflux for 5 min
12. concentrationthen concentrated under reduced pressure
13. customThe residue was purified by chromatography
14. washeluting with CH2Cl2
15. customfollowed by crystallisation from CH2Cl2/hexane