Di(tert-butyl) (2S,4S)-4-hydroxy-6-oxo-1,2-piperidinedicarboxylate could be produced through the following synthetic routes.

A. 2-tert-Butoxycarbonylamino-4-(2,2-dimethyl-4,6-dioxo-[1,3]dioxan-5-yl)-4-oxo-butyric acid tert-butyl ester. A one-necked, 500-mL, round-bottomed flask containing a magnetic stir bar and fitted with a three-way stopcock fitted with a rubber septum and an argon inlet is charged with 15.0 g (51.85 mmol) of N-α-tert-butoxycarbonyl-L-aspartic acid α-tert-butyl ester (Boc-L-Asp-Ot-Bu) and 150 mL of . The resulting solution is cooled in an ice bath at 0 °C (ice bath temperature) whereupon 7.85 g (54.44 mmol, 1.05 equiv) of () and 9.50 g (77.78 mmol, 1.5 equiv) of 4-dimethylaminopyridine (P) are added. N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochoride (EDC·HCl) (14.91 g, 77.78 mmol, 1.5 equiv) is then added portion-wise to the reaction mixture at 0 °C over 5 min. The three-way adapter is returned to the neck and reaction mixture is allowed to warm to room temperature and is stirred under argon for 3 h. The solution is diluted with 50 mL of dichloromethane before being transferred to a 500-mL separatory funnel and is then washed successively with two, 150-mL portions of 1 M aq KHSO₄ solution and 150 mL of brine. The organic layer is dried over Na₂SO₄ (25–30 g), then is filtered through a cotton plug in a funnel, collected in a 500-mL flask and concentrated by rotary evaporation (40 °C, 6 mm Hg) to provide 21.5 g of crude 2 as a clear, pale-yellow oil.

B. Di(tert-butyl) (2S)-4,6-dioxo-1,2-piperidinedicarboxylate. (330 mL) is added to the 500-mL flask containing 2, which is then equipped with a magnetic stir bar and a reflux condenser. The solution is heated in an oil bath at 80 °C (bath temperature) for 3 h. The solution is allowed to cool before being transferred to a 1-L separatory funnel and is washed successively with 200 mL of 1 N aq KHSO₄ solution and 200 mL of brine. The organic layer is dried over Na₂SO₄ (25–30 g), filtered through a cotton plug in a funnel, and concentrated by rotary evaporation (34–40 °C, 6 mm Hg). The residual crystalline material is slurried in 100 mL of cyclohexane, then is collected by filtration in a Hirsch funnel and is washed with two, 50-mL portions of cyclohexane and then dried under reduced pressure (40 °C, 6 mm Hg) to afford 12.61 g (78%, 2 steps from 1) of dioxopiperidine 3 as a white solid.

C. Di(tert-butyl) (2S,4S)-4-hydroxy-6-oxo-1,2-piperidinedicarbox-ylate. A two-necked, 500-mL, round-bottomed flask fitted with a rubber septum, argon needle inlet and thermometer is charged with dioxopiperidine 3 (12.61 g, 40.25 mmol) and 150 mL of dichloromethane. The resulting solution is cooled in an ice bath at 0 °C (bath temperature) while 25 mL of AcOH is added. borohydride (NaBH₄) (4.57 g, 120.75 mmol, 3.0 equiv) is then added portion-wise to the reaction mixture at such a rate as to keep the internal temperature below 10 °C. The reaction mixture is allowed to warm to room temperature and is stirred for 12 h. The reaction mixture is neutralized with 150 mL of 1 M aq KHSO₄ solution and then is transferred to a 500-mL separatory funnel. The aqueous phase is separated and the organic layer is dried over Na₂SO₄ (25–30 g), filtered through a cotton plug in a funnel, and concentrated by rotary evaporation (40 °C, 6 mm Hg). Dichloromethane (250 mL) is added to the 500-mL flask, which is then equipped with a magnetic stir bar. The resulting solution is cooled in an ice bath at 0 °C while 25 mL AcOH is added. (NaBH₄) (1.52 g, 40.25 mmol, 1.0 equiv) is then added portion-wise to the reaction mixture over 5 min. The reaction mixture is allowed to warm to room temperature and is stirred for 4 h. The reaction mixture is neutralized with 100 mL of a 1 M aq KHSO₄ solution and is transferred to a 500-mL separatory funnel. The aqueous phase is separated and the organic layer is dried over Na₂SO₄ (25–30 g), filtered through a cotton plug in a funnel, and concentrated by rotary evaporation (40 °C, 6 mm Hg). The residue is dissolved in 200 mL of ethyl acetate, and the solution transferred to a 500-mL separatory funnel where it is washed successively with two, 150-mL portions of 1 M aq KHSO₄ solution and two, 150-mL portions of sat. aq sodium bicarbonate solution and 150 mL of brine. The organic layer is dried over Na₂SO₄ (25–30 g), filtered through a cotton plug in a funnel, and concentrated by rotary evaporation (40 °C, 6 mm Hg). The residual crystalline solid is dissolved in 23 mL of dichloromethane. (150 mL) is slowly added and the resulting slurry is triturated for 1 h. The white solid that precipitates is collected by filtration, then is washed with 50 mL of diisopropyl ether, 50 mL of cyclohexane and then is dried under reduced pressure (25 °C, 6 mm Hg and then 0.04 mm Hg) to afford 6.25 g (49.3%) of 4. The filtrate is concentrated and the residue is dissolved in 9 mL dichloromethane. After addition of diisopropyl ether (100 mL) and a magnetic stir bar, the mixture is stirred for 10 h at room temperature to afford a second crop (1.60 g), which is collected by filtration and is combined with the first crop of crystals to give a final yield of 7.85 g (62 %).