Preparation method of 2-tert-butyl-7-methyl-5-oxa-2,8-diazaspirane-[3,5]nonane-2,7-dicarboxylic acid

[0010] Example 1: a. Compound 1 (430g, 1.77mol) was dissolved in 3L of tetrahydrofuran, under the protection of nitrogen, the reaction temperature was controlled at -78°C to -50°C, and n-butyllithium (125g, 1.95 mol). After the dropwise addition, the reaction temperature was maintained and stirring was continued for 1-2 hours. Benzyl chloroformate (322.8 g, 1.86 mol) was dissolved in 1 L of tetrahydrofuran, and the reaction temperature was controlled at -78°C to -50°C, and added dropwise to the reaction solution. After the dropwise addition, the reaction temperature was maintained and stirring was continued for 2-4 hours. TLC (petroleum ether / ethyl acetate volume ratio=2 / 1) showed that the reaction was complete. The reaction solution was poured into saturated aqueous ammonium chloride (5 L), and extracted with ethyl acetate (3 L x 3). The organic phases were combined, dried over sodium sulfate, filtered, and concentrated by distillation under reduced pressure to obtain a cr...

[0015] Example 2: a. Compound 1 (4300g, 17.7mol) was dissolved in 25L of tetrahydrofuran, under the protection of nitrogen, the reaction temperature was controlled at -78°C to -50°C, and n-butyllithium (1250g, 19.5 mol). After the dropwise addition, the reaction temperature was maintained and stirring was continued for 1-2 hours. Benzyl chloroformate (3228 g, 18.6 mol) was dissolved in 5 L of tetrahydrofuran, and the reaction temperature was controlled at -78°C to -50°C, and added dropwise to the reaction solution. After the dropwise addition, the reaction temperature was maintained and stirring was continued for 2-4 hours. TLC (petroleum ether / ethyl acetate volume ratio=2 / 1) showed that the reaction was complete. The reaction solution was poured into saturated aqueous ammonium chloride solution (35 L), and extracted with ethyl acetate (15 L x 3). The organic phases were combined, dried over sodium sulfate, filtered, and concentrated by distillation under reduced pressure t...