Potassium Carbonate → Tradipitant

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

Add 1-azidomethyl-3,5-bistrifluoromethylbenzene (3.73 g, 13.8 mmol) and potassium carbonate (5.73 g, 41.4 mmol) to a solution of (2-chlorophenyl)-[2-(2-hydroxy-2-pyridin-4-yl-vinyl)pyridin-3-yl]methanone phosphate (6.0 g, 13.8 mmol) in DMSO (16 mL). Heat to 40° C. and stir for approximately 20-24 h. Cool the reaction mixture to ambient temperature, and add the mixture to CH2Cl2 (75 mL) and 1 N NaOH (75 mL). Separate the layers, and extract the aqueous layer with CH2Cl2 (50 mL). Separate the layers, combine the organic layers and extract the combined organic layers with 1 N NaOH (2×50 mL). Add MgSO4 and acid-washed carbon (1.2 g), stir for 20 min and filter through Celite®. Concentrate the filtrate to a total weight of approximately 25 g. Add heptane (75 mL) dropwise over approximately 45 min. Seed the solution with the title compound if necessary. Stir the resulting slurry for 1 h and then filter to obtain the title compound. Dry the title compound, then add it to isopropanol (36 mL). Heat the mixture until the solid dissolves (approx. 65° C.). Allow the solution to cool to ambient temperature. Stir the resulting slurry for approximately 3 hours. Cool the slurry in an ice/water bath and stir for 2 h. Filter and dry to afford the title compound as a white solid. MS(IS) 588 (M+1). TLC (3% MeOH/CH2Cl2) Rf=0.17. 1H NMR (400 MHz, CDCl3): 5.46 (s, 2H); 7.19 (m, 5H); 7.36 (dd, 1H, J=4.9, 7.8); 7.45 (s, 2H); 7.59 (m, 1H); 7.83 (s, 1H); 7.93 (dd, 1H, J=1.5, 7.8); 8.56 (dd, 1H, J=1.5, 4.9); 8.70 (d, 2H, J=5.9).

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