反应详情

A solution of 3-(3-oxocyclobutyl)propanoic acid (157 mg, 0.696 mmol) and 4-chloro-5-(trifluoromethyl)benzene-1,2-diamine (146 mg, 0.696 mmol) in N,N-dimethylformamide (2.5 mL) was cooled at 0° C. The solution was treated with N,N-diisopropylethylamine (0.364 mL, 2.09 mmol) dropwise followed by N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (291 mg, 0.765 mmol) in one portion. The solution was allowed to stir and slowly warm to room temperature. After 40 h, the reaction mixture was concentrated partially under high vac. The remaining brown liquid was taken up in 25 mL EA and 15 mL 1/1 sat NaHCO3/H2O and extracted. The aqueous phase was washed with two 15 mL portions of ethyl acetate and the combined organic phase was washed with 30 mL portions of H2O and brine. The organic phase was dried over MgSO4, filtered and concentrated to yield a tannish brown viscous oil/glass. The crude material was purified by flash chromatography (40 g silica gel, 50-80% EA/hept) to yield the title compound (72 mg, 31%) as a slightly tan glass/stiff foam: MS (ESI+) for C14H14ClF3N2O2 m/z 335.2 (M+H)+; MS (ESI−) for C14H14ClF3N2O2 m/z 333.3 (M−H)−; HPLC purity 78.2% (ret. time, 3.56 min).

1. concentrationthe reaction mixture was concentrated partially under high vac
2. extractionextracted
3. washThe aqueous phase was washed with two 15 mL portions of ethyl acetate
4. washthe combined organic phase was washed with 30 mL portions of H2O and brine
5. dry with materialThe organic phase was dried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated
8. customto yield a tannish brown viscous oil/glass
9. customThe crude material was purified by flash chromatography (40 g silica gel, 50-80% EA/hept)