Synthesis
1. 490 kg (370 L) of anhydrous dichloromethane and 1320 kg (753 L) of chlorosulfonic acid were added to a reactor, ensuring that the ratio of dichloromethane to chlorosulfonic acid was 0.5:1 by volume.
2. The temperature of the mixture was adjusted to 10-15 °C and 665.0 kg of citric acid monohydrate was added at a rate of 1.25 kg/min, maintaining the reaction temperature between 10-15 °C.
3. after the addition is complete, continue to stir the reaction mixture at 10-15 °C until no gas is released (at least 6 hours).
4. Cool the reaction mixture to 3-5°C and slowly add 640 kg (800 L) of anhydrous methanol, controlling the internal temperature to no more than 25°C.
5. Warm the reaction mixture to 30-35 °C and stir for 2 hours to complete the esterification reaction.
6. Cool the reaction mixture to 10-12 °C. Slowly add 1300 L of water, controlling the temperature to no more than 15 °C.
7. 800 mL of dichloromethane was added, stirred for 15 minutes and then allowed to stand for 30 minutes to separate the organic phase.
8. The aqueous phase was extracted three times with 400 mL of dichloromethane and the organic phases were combined.
9. The organic phase was washed sequentially with 1000 L of water and 75 kg of sodium bicarbonate in 1000 L of aqueous solution, adjusting the pH to about 7.
10. The organic phase was separated, washed twice with 750 mL of water and evaporated under vacuum. Evaporation conditions: 3-5 kPa, internal temperature not exceeding 75°C.
11. 535 kg of dimethyl 3-oxoglutarate was obtained and used in subsequent reactions without further purification.
12. Gas chromatography analysis conditions: HP-6850 gas chromatograph, HP-1.25 m x 0.32 mm column, film thickness 0.17 μm, carrier gas is hydrogen, programmed temperature increase: 80 ℃ held for 5 minutes, 10 ℃/min to 200 ℃ and held for 8 minutes, detector FID 280 ℃, injector 200 ℃.
13. Expected retention times: 1.18 min for methyl acetoacetate, 5.77 min for dimethyl 3-oxoglutarate, 8.15 min for enol ethers, 10.00 min for trimethyl aconite, 10.42 min for trimethyl citrate, 18.76 min for isosorbic acid derivatives.
14. Area normalization results: methyl acetoacetate 0.31%, dimethyl 3-oxoglutarate 98.33%, enol ether 0.81%, trimethylaconate 0.28%, trimethyl citrate 0.19%, isosorbic acid derivatives not detected, and other contaminants (>0.2%) not detected.
