153-61-7

Method 1: In a 10L four-necked round-bottom flask, add 500g of 7-aminocephalosporanic acid (7-ACA) and 5000ml of dichloromethane. While stirring, add a saturated aqueous solution containing 170g of sodium bicarbonate and 5.0g of tetrabutylammonium bromide. Control the temperature to -5～0℃, and add 308g of thiophene acetyl chloride dropwise, stopping the addition over 50～60 minutes. After reacting at a constant temperature for 4 hours, the mixture was filtered, the filter cake was washed with dichloromethane, filtered under vacuum, and dried to obtain (6R,7R)-3-[(acetoxy)methyl]-7-[2-(2-thienyl)acetamido]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid (cephalothinic acid). Method 2: In a 500ml reaction flask, under nitrogen protection, add 50g of 7-ACA, 300ml of dichloromethane, and 53g of N,O-bis(trimethylsilyl)acetamide (BSA). Stir and dissolve at 25-30℃, cool to 10℃, and add 33.1g of 2-thiophene acetyl chloride dropwise over 60 minutes. After the addition is complete, maintain the reaction temperature for 1-2 hours. Dichloromethane is evaporated under reduced pressure. After evaporating the dichloromethane to dryness, add 300ml of purified water and stir rapidly. A solid precipitates, is filtered, and the product is washed twice with 200ml of purified water. The product is then dried under reduced pressure at 40℃. 67g of the white compound (6R,7R)-3-[(acetoxy)methyl]-7-[2-(2-thienyl)acetamido]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid is obtained. Yield: 92.0%.