反应详情

200 mg (0.641 mmol) of (+/−)-tert-butyl 1-[(3-amino-4-chlorophenyl)(methoxy)methyl]cyclopropanecarboxylate and 188 mg (0.706 mmol) of (+)-(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoic acid were dissolved in 2.3 ml of DMF and 0.7 ml of pyridine, and 293 mg (0.770 mmol) of HATU were added at RT. The reaction mixture was stirred at RT overnight. Another 0.6 eq. of (+)-(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoic acid was then added, and the reaction mixture was stirred at 45° C. for 14 h. After cooling, the mixture was diluted with ethyl acetate and the solution was washed with 1 N hydrochloric acid and saturated sodium chloride solution, dried over magnesium sulphate and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 30:1). This gave 168 mg of the target compound (39.9% of theory).

1. stirringthe reaction mixture was stirred at 45° C. for 14 h
2. temperatureAfter cooling
3. washthe solution was washed with 1 N hydrochloric acid and saturated sodium chloride solution
4. dry with materialdried over magnesium sulphate
5. concentrationconcentrated under reduced pressure
6. customThe residue was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 30:1)