Synthesis
600 mL of N,N-dimethylformamide (DMF) was added to the reaction flask and the temperature of the reaction system was lowered to 0°C to 5°C. Subsequently, 179.5 g (0.55 mol) of (2S,4S)-1-carboxy-4-mercaptopyrrolidine (Formula VI) was added. Next, 66.8 g (0.66 mol) of diisopropylethylamine was added and the reaction mixture was stirred for 10 minutes. Then, 89.7 g (1.10 mol) of dimethylamine hydrochloride was added, and the reaction temperature was maintained between 0 °C and 5 °C, and the reaction continued to be stirred for 3 hours. Upon completion of the reaction, 500 mL of ice water was quickly added to the reaction mixture and stirred to precipitate a large amount of solid. The solid product was collected by filtration and the filter cake was washed with 200 mL of water. Finally, the product was dried under reduced pressure at 65 °C for 15 h to afford 179.4 g (2S,4S)-1-p-nitrobenzyloxycarbonyl-2-(N,N-dimethylcarbamoyl)-4-mercapto-pyrrolidine (Formula VII) in 92.3% molar yield and 99.3% HPLC purity. The mass spectral data of compound VII were as follows: molecular formula C15H19N3O5S, molecular weight 353.4, [M+H]+: 354.6.
References
[1] Patent: CN105439932, 2016, A. Location in patent: Paragraph 0075; 0076; 0077
[2] Patent: CN105439933, 2016, A. Location in patent: Paragraph 0062; 0063; 0064