General procedure: Example 1: Preparation of Intermediate 1: tert-butyl 4,4-difluoropiperidine-1-carboxylate
To a solution of N-tert-butoxycarbonyl-4-piperidone (10 g; 0.05 mol) in anhydrous dichloromethane (80 ml) at 40 °C, diethylamino sulfur trifluoride (DAST, 3 eq.) was slowly added. The reaction mixture was stirred at 20 °C for 4 hours. Subsequently, the mixture was brought back to room temperature and carefully poured into saturated aqueous sodium bicarbonate solution. The aqueous phase was extracted with dichloromethane (3 x 70 ml) and the combined organic phases were washed with deionized water and dried over anhydrous sodium sulfate. After concentration under reduced pressure, a light yellow oily product was obtained in 95% yield.
1H NMR (CDCl3) δ: 3.52-3.58 (m, 4H), 1.87-2.0 (m, 4H), 1.49 (s, 9H).
