N-tert-Butoxycarbonyl-l-leucinal (CAS NO.: ), with other names like Boc-L-leucinal, could be produced through the following synthetic methods.

A. Boc-L-leucine N-methyl-O-methylcarboxamide. A 1-L, three-necked, round-bottomed flask is equipped with a mechanical stirrer, an electronic digital thermometer, and a graduated addition funnel. The flask is charged with 39.1 g (0.4 mol) of N,O-dimethylhydroxylamine hydrochloride and 236 mL of methylene chloride. The suspension is stirred and cooled to 2°C with an ice–water bath. N-Methylpiperidine., 48.8 mL (0.41 mol), is placed in the addition funnel and added dropwise while the temperature is maintained at 2° ± 2°C. A clear colorless solution results which is kept cold and used in the following reaction.

A 5-L, three-necked, round-bottomed flask is equipped with a mechanical stirrer, a thermometer, and an addition funnel with drying tube. The flask is charged with 100 g (0.4 mol) of Boc-L-leucine hydrate, 458 mL of tetrahydrofuran, and 1.8 L of methylene chloride. A clear solution results on stirring, which is cooled to -20° ± 2°C by immersing the flask in a dry ice–2-propanol bath. N-Methylpiperidine, 48.8 mL (0.41 mol), is placed in the addition funnel and added rapidly to the mixture, while the temperature is allowed to rise to -12° ± 2°C. , 31 mL (0.4 mol), is then placed in the addition funnel and added rapidly to the mixture with good stirring, while the temperature is kept at -12° ± 2°C. Two minutes later the solution of N,O-dimethylhydroxylamine, prepared as described earlier, is added. The cooling bath is removed and the clear solution allowed to warm to room temperature over 4 hr. The solution is again cooled to 5°C and extracted with two 500-mL portions of aqueous 0.2 N hydrochloric acid and two 500-mL portions of aqueous 0.5 N sodium hydroxide. The solution is washed with 500 mL of saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated on a rotary evaporator at a bath temperature of 30–35°C. The residue is further evacuated on an oil pump to constant weight. The residual colorless syrup weighs 100–102 g (91–93%), [α]_D23 −24 to −25°(1.5% in methanol).

B. N-tert-Butoxycarbonyl-L-leucinal (CAS NO.: ): Boc-L-leucinal. A 5-L, four-necked, round-bottomed flask is equipped with an efficient mechanical stirrer, a thermometer, a pressure-equalizing addition funnel, and an air-cooled condenser fitted with an argon blanket adapter. The flask is charged under an argon blanket with 17.7 g (95% pure, 0.44 mol) of lithium aluminum hydride, and 1.5 L of anhydrous ethyl ether. The gray suspension is stirred at room temperature for 1 hr or until most of the solid is finely dispersed. The flask is immersed in a dry ice–2-propanol bath and the suspension cooled to -45°C. A solution of the Boc-L-leucine N-methyl-O-methycarboxamide, obtained in Part A, in 300 mL of anhydrous ethyl ether is placed in the addition funnel and added to the lithium aluminum hydride suspension in a steady stream while the reaction temperature is maintained -35° ± 3°C. The cooling bath is removed and the mixture is stirred and allowed to warm to +5°C. The mixture is once again cooled to -35°C and a solution of 96.4 g (0.71 mol) of potassium bisulfate in 265 mL of deionized water is placed in the addition funnel. This is added cautiously at first and then rapidly, while the temperature is allowed to rise to -2° ± 3°C. The cooling bath is removed and the mixture stirred for 1 hr. The reaction mixture is filtered through a 2-in. pad of Celite. The filter cake is washed with two 500-mL portions of ethyl ether. The combined ether layers are washed in sequence with three 350-mL portions of cold (5°C) 1 N hydrochloric acid, two 350-mL portions of saturated aqueous sodium bicarbonate solution, and 350 mL of saturated sodium chloride solution. The organic solution is dried over magnesium sulfate and evaporated on a rotary evaporator (bath at 30°C). The residual, slightly cloudy syrup weighs 69–70 g (87–88%), [α]²³ −49 to −51° (1.65% in methanol). The product is stored in a freezer (-17°C) prior to use. It solidifies readily at 5°C.