反应详情

2-(1H-Benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (6.10 g) is added to a solution of 4-oxazol-5-yl-benzoic acid (3.00 g) and ethyldiisopropylamine (5.56 mL) in N,N-dimethylformamide (50 mL) at room temperature. The solution is stirred for 10 min prior to the addition of 4-cyclopropylamino-piperidine-1-carboxylic acid tert-butyl ester (4.57 g). The resulting mixture is kept at room temperature over night. The mixture is treated with activated charcoal and filtered through a pad of basic aluminum oxide. The pad is washed with N,N-dimethylformamide/methanol (9:1) and the combined filtrates are concentrated in vacuo. The residue is dissolved in 1,4-dioxane (35 mL), a 4 M solution of hydrogen chloride in 1,4-dioxane (20 mL) is added and the resulting mixture is stirred at room temperature for 2 h. The solvent is evaporated and the residue is taken up in water. The resulting mixture is washed with dichloromethane, basified with NaOH solution and extracted with dichloromethane. The combined extracts are dried over Na2SO4 and concentrated in vacuo. The residue is triturated with diethyl ether to afford the title compound. LC (method 1): tR=0.70 min; Mass spectrum (ESI+): m/z=312 [M+H]+.

1. waitThe resulting mixture is kept at room temperature over night
2. filtrationfiltered through a pad of basic aluminum oxide
3. washThe pad is washed with N,N-dimethylformamide/methanol (9:1)
4. concentrationthe combined filtrates are concentrated in vacuo
5. dissolutionThe residue is dissolved in 1,4-dioxane (35 mL)
6. additiona 4 M solution of hydrogen chloride in 1,4-dioxane (20 mL) is added
7. stirringthe resulting mixture is stirred at room temperature for 2 h
8. customThe solvent is evaporated
9. washThe resulting mixture is washed with dichloromethane
10. extractionextracted with dichloromethane
11. dry with materialThe combined extracts are dried over Na2SO4
12. concentrationconcentrated in vacuo
13. customThe residue is triturated with diethyl ether