N-Benzyltropinone

542-05-2

100-46-9

28957-72-4

1. To a non-homogeneous solution of 2,5-dimethoxytetrahydrofuran (82.2 g, 0.622 mol) in water (170 mL) was slowly added concentrated hydrochloric acid (30 mL) under stirring conditions. 2. In another flask, benzylamine (100 g, 0.933 mol) was dissolved in water (350 mL), cooled to 0 °C (ice bath) and concentrated hydrochloric acid (92 mL) was added slowly. 3. The 2,5-dimethoxytetrahydrofuran solution was stirred for 20 minutes and diluted with water (250 mL), followed by the sequential addition of the benzylamine solution, an aqueous (400 mL) solution of 1,3-acetone dicarboxylic acid (100 g, 0.684 mol), and an aqueous (200 mL) solution of sodium hydrogensulphate (44 g, 0.31 mol). 4. the pH of the reaction mixture was adjusted from 1 to about 4.5 using a 40% NaOH solution. 5. The resulting cloudy light yellow solution was stirred overnight. 6. The solution was acidified from pH 7.5 to 3 with 50% hydrochloric acid, heated to 85°C and stirred for 2 hours. 7. After cooling to room temperature, the solution was alkalized to pH 12 with 40% NaOH solution and extracted with dichloromethane (3 x 500 mL). 8. The organic layers were combined, washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give the title intermediate as a viscous brown oil (~95% purity based on HPLC analysis). 9. The structure of the product was confirmed by 1H-NMR (CDCl3) and mass spectrometry ([M+H]+ C14H17NO calculated value 216.14; measured value 216.0).