The synthetic process of 1,1-Dimethylethyl (S)-4-formyl-2,2-dimethyl-3-oxazolidinecarboxylate (CAS NO. ) contains 4 steps. The synthetic route is as follows:

A. Synthesis of N-[(1,1-Dimethylethoxy)carbonyl]-L-serine (2). A 250-mL, three-necked, round-bottomed flask, containing a magnetic stirring bar, is equipped with a dropping funnel, reflux condenser protected from moisture by a calcium chloride-filled drying tube and a rubber septum. The dropping funnel is charged with 23 mL of . Caution! Acetyl chloride is a reactive substance that must be handled in a fume hood . The flask is charged with 150 mL of methanol and cooled with an ice-water bath under nitrogen. Acetyl chloride is added dropwise over a period of 8 min. The solution is stirred for a further 5 min, then solid 99% (L)-serine, 1, (12.0 g, 114 mmol) is added in one portion and the solution is slowly heated to reflux. The reflux is continued for 2 hr, then the solution is allowed to cool to room temperature and the solvent is removed under reduced pressure to give 17.5-17.7 g of crude methyl serinate hydrochloride (98-99% yield) as a white crystalline solid that is used without further purification.

A 500-mL, three-necked, round-bottomed flask, is equipped with a magnetic stirring bar, thermometer, reflux condenser protected from moisture by a calcium chloride-filled drying tube, and a pressure-equalizing dropping funnel that is connected to a nitrogen flow line and is charged with a solution of 97% di-tert-butyl dicarbonate (14.3 g, 63.6 mmol) in tetrahydrofuran (100 mL). Methyl serinate hydrochloride (10.0 g, 64.3 mmol) is placed in the flask and suspended in tetrahydrofuran (200 mL) and 99% triethylamine (14.0 g, 138 mmol). The resulting white suspension is cooled with an ice-water bath and the solution of di-tert-butyl dicarbonate is added dropwise over a period of 1 hr. After 10 min of additional stirring, the ice-water bath is removed and the suspension is stirred overnight (14 hr) at room temperature, then warmed at 50°C for a further 3 hr. The solvent is removed under reduced pressure and the residue is partitioned between diethyl ether (200 mL) and saturated aqueous bicarbonate solution (250 mL). The aqueous phase is extracted with three 150-mL portions of diethyl ether . The combined organic phases are dried with anhydrous sodium sulfate and concentrated under reduced pressure to give 13.4-14.0 g (95-99% crude yield) of N-Boc-L-serine methyl ester as a colorless oil that is used without further purification.

B. Synthesis of 3-(1,1-Dimethylethyl) 4-methyl-(S)-2,2-dimethyloxazolidine-3,4-dicarboxylate (3). To a solution of N-Boc-L-serine methyl ester (10.0 g, 45.6 mmol) in acetone (165 mL) is added 2,2-dimethoxypropane (50 mL, 400 mmol) and boron trifluoride etherate (BF₃^.OEt₂, 0.35 mL, 2.8 mmol). The resulting orange solution is stirred at room temperature for 2.5 hr when TLC analysis indicates the reaction to be complete. The reaction mixture is treated with 0.9 mL of 99% triethylamine and the solvent is removed under reduced pressure. The residual brown syrup is partitioned between diethyl ether (150 mL) and saturated aqueous sodium bicarbonate solution (250 mL). The aqueous layer is extracted with diethyl ether (2 × 150 mL) and the combined organic phases are dried with anhydrous sodium sulfate and concentrated under reduced pressure (7 mm and 65°C bath temperature) to give 10.4-10.8 g (88-91% crude yield) of oxazolidine methyl ester 3 as a pale yellow oil. Analysis of crude 3 by 1H NMR indicates a chemical purity of > 95%. The product can be used without further purification.

C. Synthesis of N-[(1,1-Dimethylethoxy)carbonyl]-N,O-isopropylidene-L-serinol (4). A 250-mL, two-necked, round-bottomed flask is equipped with a magnetic stirring bar, reflux condenser bearing a drying tube and a pressure-equalizing dropping funnel fitted with a rubber septum. The flask is charged with 100 mL of tetrahydrofuran and 2.16 g (57.0 mmol) of lithium aluminum hydride. While the suspension in the flask is stirred, a solution of the oxazolidine ester 3 (9.90 g, 38.2 mmol) in tetrahydrofuran (50 mL) is added dropwise over 20 min. The dropping funnel is washed with two 3-mL portions of tetrahydrofuran and the suspension is stirred for an additional 20 min, when TLC analysis shows the complete formation of the alcohol 4. The reaction mixture is cooled with an ice-water bath while 20 mL of a 10% aqueous potassium hydroxide solution is added dropwise over 10 min. Caution! The reaction is exothermic. The mixture is stirred for 1 hr at room temperature, then the white precipitate is removed by filtration through a Celite pad and the pad is rinsed with three 30-mL portions of diethyl ether . The combined organic filtrates are washed with 100 mL of aqueous phosphate buffer (pH 7), and the aqueous layer is extracted with diethyl ether (3 × 30 mL). The combined organic phases are dried with anhydrous sodium sulfate and concentrated under reduced pressure to give 8.20-8.48 g (93-96% crude yield) of a pale yellow oil. The crude product that solidifies on cold storage (mp 35-38°C) is used without further purification. Analysis of crude alcohol 4 by 1H NMR indicates a chemical purity of > 95%.

D. Synthesis of 1,1-Dimethylethyl (S)-4-formyl-2,2-dimethyl-3-oxazolidinecarboxylate (5). A 250-mL, three-necked, round-bottomed flask, containing a magnetic stirring bar is equipped with a low-temperature thermometer and two equalizing dropping funnels. One of these is connected to a nitrogen flow line and is charged with a solution of N-Boc-L-serinol 4 (8.0 g, 34.6 mmol) in methylene chloride (60 mL), the other is charged with a solution of dimethyl sulfoxide (8.10 g, 103.71 mmol) in 10 mL of methylene chloride. The flask is charged with a solution of oxalyl chloride (6.58 g, 51.9 mmol) in 80 mL of methylene chloride , then cooled to -78°C in a CryoCool bath. Caution! Oxalyl chloride is a reactive substance that must be handled in a fume hood. When the solution in the flask is at -78°C, dimethyl sulfoxide is added dropwise over 25 min, while the temperature of the reaction mixture rises to -70°C. At the end of the addition the reaction solution is warmed to -60°C over a period of 20 min, then the N-Boc-L-serinol 4 is added dropwise over 50 min and the reaction temperature rises to -55°C. The dropping funnel is washed with two 5-mL portions of methylene chloride , then charged with a solution of N,N-diisopropylethylamine (36 mL, 200 mmol) in 5 mL of methylene chloride and the reaction solution is warmed to -45°C over a period of 30 min. N,N-Diisopropylethylamine is added over 5 min, then the reaction flask is removed from the CryoCool bath and allowed to warm to 0°C over 10 min. The reaction solution is transferred to a 500-mL separatory funnel charged with 130 mL of ice-cold 1 M hydrochloric acid solution. The two phases are separated, the aqueous phase is extracted with methylene chloride (3 × 30 mL), and the combined organic phases are washed with pH 7 aqueous phosphate buffer (4 × 80 mL), then dried with anhydrous sodium sulfate and concentrated under reduced pressure to give 7.89 g (99% crude yield) of the aldehyde 5 as a clear yellow oil. Analysis of crude aldehyde 5 by 1H NMR indicates a chemical purity of > 95%.