反应详情

(3-tert-Butoxycarbonylamino-2′-trifluoromethoxy-biphenyl-4-yl)-carbamic acid tert-butyl ester (573 mg, 1.22 mmol, as prepared in the previous step) was placed in a mL vial equipped with a magnetic stir bar. DCM (10 mL) and TFA (5 mL) were added, and the mixture stirred at rt for 12 h. The solvent was removed under reduced pressure, and the residue was dissolved in DCM and washed with 2M aq NaOH. The organic extract was dried over MgSO4 and concentrated in vacuo. The residue was dissolved in AcOH (5 mL) and placed in an 8 mL vial equipped with a magnetic stir bar. The mixture was cooled to 0° C., treated with methyl-2,2,2-trichloroacetimidate (0.167 mL, 1.35 mmol) via syringe, and stirred at rt for 3 days. The solvent was removed under reduced pressure. The crude product was purified by column chromatography using a 12-g SiO2 pre-packed column eluting with EtOAc/hexanes, 0:1 to 2:5, v/v over 30 min, yielding 409 mg (85%) of the desired compound. 1H-NMR (400 MHz, d4-MeOH) δ: 7.71-7.77 (m, 2H), 7.52-7.57 (m, 1H), 7.39-7.51 (m, 4H).

1. customvial equipped with a magnetic stir bar
2. customThe solvent was removed under reduced pressure
3. dissolutionthe residue was dissolved in DCM
4. washwashed with 2M aq NaOH
5. extractionThe organic extract
6. dry with materialwas dried over MgSO4
7. concentrationconcentrated in vacuo
8. dissolutionThe residue was dissolved in AcOH (5 mL)
9. customvial equipped with a magnetic stir bar
10. temperatureThe mixture was cooled to 0° C.
11. stirringstirred at rt for 3 days
12. customThe solvent was removed under reduced pressure
13. customThe crude product was purified by column chromatography
14. washeluting with EtOAc/hexanes, 0:1 to 2:5, v/v over 30 min