Synthesis
The general procedure for the synthesis of (6R,7R)-3-(chloromethyl)-8-oxo-7-(2-phenylacetamido)-5-thiophene-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid-4-methoxybenzyl ester, using the compound (CAS:131903-39-4) as a starting material, was as follows: in 2000 mL dioxane, 120 g of sodium bicarbonate ( 1.43 mol) and 200 g of azodioxanone sulfinic acid intermediate (0.336 mmol) and stirred at 10 to 15 °C. 30 g of chlorine gas (0.422 mol) was slowly passed for about 3 h. The reaction progress was monitored by HPLC until the peak area of the feedstock dropped below 0.5%. The passage of chlorine gas was stopped, sodium bicarbonate was removed by filtration and dioxane was recovered under vacuum. 2000 mL of methanol was added to dissolve the residue and the reaction temperature was maintained at 0-5 °C. Subsequently, a 900 mL methanol solution of 18 g sodium methanolate (0.34 mol) was added and the reaction was maintained at 0~5 °C for 30 min. The pH of the reaction system was adjusted to 4~6 with 10% hydrochloric acid and stirring was continued at 0~5°C for 1 hour. After completion of the reaction, the product was collected by filtration, washed with water and methanol sequentially, and dried to give 125 g of GCLE in 76.3% yield and ≥94% purity.
![1-Azetidineacetic acid, α-[1-(chloromethyl)ethenyl]-2-(2,2-dioxido-2-phenyldithio)-4-oxo-3-[(2-phenylacetyl)amino]-, (4-methoxyphenyl)methyl ester, (αR,2R,3R)-](/CAS/20240320/GIF/131903-39-4.gif)
