Doripenem intermediate compound, preparation process therefor and use thereof, and preparation process for doripenem

A process for preparing a doripenem intermediate compound represented by formula (XIV),

• wherein, PNB is p-nitrobenzyl, and HX is selected from hydrochloric acid, hydrobromic acid, nitric acid, acetic acid, formic acid, propionic acid, n-butyric acid, isobutyric acid, trichloroacetic acid, benzoic acid, salicylic acid, lactic acid, sulfuric acid, phosphoric acid, phosphorous acid, oxalic acid, maleic acid, succinic acid, fumaric acid, malic acid, tartaric acid, citric acid;
• and
• when HX is a monobasic acid, n=1;
• and when HX is a polybasic acid, n=2, comprising:
• (1-1) reacting a parent nucleus compound (II) of carbapenem antibiotic compounds and a side-chain compound (XV) of doripenem at −60˜15° C. in an organic solvent under the action of a base, wherein:
• the organic solvent is selected from one or more of acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, N,N-diethylformamide and N,N-diethylacetamide;
• the base is selected from one or more of triethylamine, N,N-diisopropylethylamine, tetramethyl guanidine and tri-n-butylamine,
• a molar ratio of the parent nucleus compound (II) of carbapenem antibiotic compounds, the side-chain compound (XV) of doripenem to the base is 1:1˜2:1˜3;
• a reaction concentration calculated based on the parent nucleus compound (II) is 0.01˜2 mol/L;
• and
• a reaction time is 3-24 hours;
• and
• (1-2) reacting a reaction mixture or product obtained in act (1-1) with a water solution containing HX at −15˜40° C. to obtain the doripenem intermediate compound represented by formula (XIV), wherein:
• a molar ratio of HX to the parent nucleus compound (II) in act (1-1) is 1˜10:1;
• a weight percent concentration of the water solution containing HX is 0.01%˜1%;
• and
• a reaction time is 3-36 hours,