反应详情

To a solution of 23.4 mg (0.102 mmol) 2-cyclopropyl-4-trifluoromethyl-benzoic acid (intermediate B2), 53.1 mg (0.139 mmol) HATU and 64 ul (0.370 mmol) N-ethyldiisopropylamine in 0.8 ml N,N-dimethylformamide, was added a solution of 20 mg (0.0925 mmol) (1RS,2RS,5SR)-8-methyl-2-phenyl-8-aza-bicyclo[3.2.1]oct-2-ylamine (intermediate A1) in 0.2 ml N,N-dimethylformamide. The mixture was stirred at room temperature overnight. The solvent was removed in vacuo. The residue was dissolved in ethyl acetate. The solution was washed once with water and twice with a saturated sodium bicarbonate solution. The aqueous layer was extracted once with ethyl acetate. The combined extracts were dried over sodium sulfate, filtered and concentrated in vacuo. The crude oil was purified with flash column chromatography on silica (5 g) eluting with a gradient formed from n-heptane and ethyl acetate (0 to 50%) to provide 10 mg (y: 25.2%) of the title compound as a colorless viscous oil. MS (m/e): 429.2 (M+H+)

1. customThe solvent was removed in vacuo
2. dissolutionThe residue was dissolved in ethyl acetate
3. washThe solution was washed once with water and twice with a saturated sodium bicarbonate solution
4. extractionThe aqueous layer was extracted once with ethyl acetate
5. dry with materialThe combined extracts were dried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe crude oil was purified with flash column chromatography on silica (5 g)
9. washeluting with a gradient
10. customformed from n-heptane and ethyl acetate (0 to 50%)