反应详情

To 20 mL of anhydrous CH2Cl2 was added 0.93 g of {2-[3-(2-Fluoro-3-methoxy-phenyl)-ureido]-1,1-dimethyl-ethyl}-carbamic acid tert-butyl ester and triethylamine (1.0 eq, 0.36 mL). N-(chlorocarbonyl) isocyanate (1.0 eq, 0.11 mL) was added to the solution in one portion. The reaction stalled after one hour, so additional triethylamine (1.0 eq, 0.36 mL) and N-(chlorocarbonyl) isocyanate was added. The reaction was determined to be complete by LC/MS after two hours. Excess isocyanate was quenched with the dropwise addition of H2O (1 mL). The reaction was then diluted with 20 mL H2O, and the organic layer was collected. The aqueous layer was extracted with CH2Cl2 (2×20 mL). The combined organics were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified via flash column chromatography and eluted with 60% EtOAc/hexanes to yield 0.65 g (59%). Rf=0.66 in 60% EtOAc/hexanes. 1H NMR (CDCl3) δ: 7.19 (dt,1H), 7.09 (dt,1H), 6.90 (dt,1H), 5.15 (ds,1H), 4.1 (q,2H), 3.92 (s,3H), 1.42 (s,9H), 1.38 (d,6H).

1. waitto be complete by LC/MS after two hours
2. customExcess isocyanate was quenched with the dropwise addition of H2O (1 mL)
3. additionThe reaction was then diluted with 20 mL H2O
4. customthe organic layer was collected
5. extractionThe aqueous layer was extracted with CH2Cl2 (2×20 mL)
6. washThe combined organics were washed with brine
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe residue was purified via flash column chromatography
11. washeluted with 60% EtOAc/hexanes
12. customto yield 0.65 g (59%)