144688-69-7

67-56-1

85909-08-6

144688-69-7

Step 2: Synthesis of tert-butyl 2-methoxypyrrolidine-1-carboxylate (51b). To a solution of anhydrous ether (250 mL) of 51a (20.0 g, 107.98 mmol) was added a toluene solution of 1 M DIBAL-H (73.426 mL, 110.14 mmol) in batches at -78 °C. The reaction mixture was stirred at -78°C for 1 hour before slowly warming to room temperature and continuing to stir overnight. Subsequently, the mixture was cooled to 0 °C and saturated ammonium chloride solution (50 mL) and 1 M Rochelle salt solution (300 mL) were added sequentially. The mixture was transferred to a 2L conical flask, additional ether was added, and the mixture was stirred vigorously for 1 hour (until the emulsion was loosened and separated). Afterwards, the mixture was transferred to a separatory funnel, and the aqueous phase was separated and discarded. The organic phase was washed sequentially with Rochelle's salt solution and saturated brine, dried over anhydrous sodium sulfate and filtered, and concentrated to give an oil. The oil was again purified by concentration with methanol. The purified oily substance was dissolved in methanol (250 mL) and p-toluenesulfonic acid monohydrate (1.0270 g, 5.3990 mmol) was added. The reaction mixture was stirred at room temperature for 48 hours and then concentrated and the residue was dissolved in dichloromethane (300 mL) and washed with saturated sodium bicarbonate solution (300 mL). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to give 20.09 g (92% yield) of the target product 51b as an oil.