1416134-48-9

1416134-60-5

144-62-7

1416134-48-9

In a 2000 mL four-necked flask fitted with a stirring device and a thermometer inserted, 500 g of ethyl acetate and 110.0 g (0.4 mol) of ethyl 5-benzyloxyiminopiperidine-2-carboxylate (III2) were added. The reaction system was cooled to -20 °C to -15 °C and 201.0 g (2.0 mol) of concentrated sulfuric acid was slowly added dropwise. After the dropwise addition was completed, the reaction continued to be stirred at -20 °C for 1 hour. Subsequently, 190.0 g (0.9 mol) of sodium triacetoxyborohydride was added in batches at -20 °C, and the reaction was stirred for 5 hours keeping the temperature in the range of -20 °C to -15 °C. Upon completion of the reaction, the temperature was controlled below 0 °C and the reaction was quenched by slow addition of 200 g of water and neutralized with ammonia to pH 7-8. The organic layer was separated and washed twice with 100 g of saturated brine. The organic phase was concentrated to recover the solvent and 320 g of ethyl acetate and 160 g of methanol were added to the residue, followed by 52.0 g (0.42 mol) of oxalic acid dihydrate. The mixture was heated to 45°C, stirred for 2 hours and then cooled to room temperature and filtered. The filter cake was washed with 100 g ethyl acetate/methanol (2:1) solvent mixture and then with 50 g ethyl acetate. All filtrates were combined for use in subsequent steps. The filter cake was dried under vacuum to give 96.3 g of the single isomer (2S,5R)-5-((benzyloxy)amino)piperidine-2-carboxylic acid ethyl ester oxalate, with 99.6% purity and 65.4% yield by chiral HPLC.