153773-82-1

202467-70-7

153773-82-1

Synthesis of (4R,5S,6S)-3-(((3S,5S)-5-((3-carboxyphenyl)carbamoyl)pyrrolidin-3-yl)thio)-6-((R)-1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo(R)), according to the methodology described in CN102731508A, based on the compound (CAS: 202467-70-7) The general procedure for the monosodium salt of [3.2.0]hept-2-ene-2-carboxylic acid was as follows: to a solvent mixture of 750 mL of ethyl acetate and 500 mL of water was added the doubly protected crystalline form of Ertapenem (10 g, 0.017 mol) prepared in Example 1. The pH was adjusted to 7.1-7.2 with 5% aqueous sodium hydroxide, followed by the addition of 15 g of palladium carbon catalyst. The hydrogenation reaction was carried out under hydrogen pressure of 20.0-30.0 MPa for 2 hours. After completion of the reaction, the catalyst was removed by filtration and the filtrate was extracted with dichloromethane (100 mL x 2) to separate the aqueous layer. The aqueous layer was adsorbed through a macroporous adsorbent resin, followed by washing the resin with 2 L of deionized water. Next, the resin was eluted with acetone solution containing 0.05 M sodium bicarbonate, and after the eluate was acidified to pH 5.5, it was concentrated by nanofiltration to 50 mL. 100 g of a solvent mixture of methanol and n-propanol (W/W = 1:1) was added to the concentrated solution, and it was further concentrated to promote crystallization. The temperature of the crystallization process was controlled at 10-20 °C, and the product was collected by filtration upon completion of crystallization. The product was dried under vacuum at <0.09 MPa for 3 h. The final product was 3.4 g of Ertapenem monosodium salt in 40.2% yield and 99.2% purity by HPLC.