Potassium Carbonate → (1α,2β,4β,5α)-9-Methyl-3-oxa-9-azatricyclo[3.3.1.02,4]nonan-7α-ol

Participants

Reaction Steps

5.45 g (0.023 mol) of scopine hydrobromide was suspended in 30 mL of DCM, and then 5 g (0.036 mol) of potassium carbonate was added. The reaction mixture was stirred at room temperature for one hour and then filtered on Goch P3 and washed with acetonitrile several times, (using about 10 ml of acetonitrile). After evaporation of the filtered solution, 2.78 g of scopine base was obtained (77.5% yield). 3.0 g (0.02 mol) of scopine base was suspended at room temperature in 27 mL of dimethylformamide, then 2.7 g (0.02 mol) of anhydrous potassium carbonate was added, and the mixture was stirred at room temperature for about 60 minutes. 4.9 g (0.02 mol) of methyl di-(2-thienyl)glycolate were dissolved in 9 mL of dimethylformamide, and, with 1.33 g (0.0096 mol) of anhydrous potassium carbonate, they were added to the reaction mixture at about 60-65° C. The suspension was heated to 65° C., under vacuum (70-100 mbar), and under nitrogen stripping (2.2-2.4 L/min) for 18 hours. At the end of the reaction the distilled DMF was re-added to the reaction mixture and other 2 volumes of DMF, for a total of 15 volumes (45 mL), were added. The reaction mixture was cooled to 0° C., and acidified to a pH of 3 with 33 mL of 2M HBr (temperature during addition below 20° C.). The obtained solution was extracted twice with 15 mL toluene, and the combined aqueous phases were then cooled to 0-5° C., and basified with 7.1 g of solid potassium carbonate to a pH of 9. After one hour at 0° C., the solid was filtered on Goch P3, and washed five times with 30 mL of water to obtain a pH of 7. The solid was dried under vacuum at 45° C. for 16 hours yielding 5.1 g (69.5% yield, 98.5% HPLC purity)

Provenance & Evidence