Beta-lactamase inhibitor intermediate and preparation method therefor

A preparation method for a β-lactamase inhibitor, comprising the following steps:

• step 1:
• in a solvent, in the presence of a base and a phase transfer catalyst, subjecting a compound of formula 56 to a benzyl esterification reaction as shown with benzyl bromide to give a compound of formula 57;
• step 2:
• in a solvent, in the presence of a base, subjecting the compound of formula 57 to a benzoylation reaction as shown with benzoyl chloride to give a compound of formula 58;
• step 3:
• in a solvent, in the presence of a base, an aqueous formaldehyde solution or paraformaldehyde, and a phase transfer catalyst, subjecting the compound of formula 58 to a reaction as shown to give a compound of formula 59;
• step 4:
• in a solvent, in the presence of a Zn/Cu or Zn/Ag reagent, subjecting the compound of formula 59 to a cyclopropanation reaction as shown with a methylating reagent to give a compound of formula 3;
• step 5:
• in a solvent, in the presence of a base, subjecting the compound of formula 3 to a ring-opening reaction as shown with trimethylsulfoxonium iodide to give compound 4;
• step 6:
• in a solvent, in the presence of a catalyst and a ligand, subjecting the compound of formula 4 to a ring-closing reaction as shown to give compound 5;
• step 7:
• in a solvent, in the presence of a base, subjecting the compound of formula 5 to a Schiff base reaction with O-phenylhydroxylamine or a salt thereof to give compound 6;
• step 8:
• (1) in a solvent, in the presence of sulfuric acid, reacting the compound of formula 6 with an acid to give a mixture A;
• and (2) adding a reducing agent to the mixture A to conduct a reduction reaction to give a compound of formula 7;
• step 9:
• adding a mixture of triphosgene and a solvent to a mixture of the compound of formula 7 and/or a salt thereof, a base and a solvent to conduct an amidation ring-closing reaction as shown to give a diazabicyclooctane compound of formula 8;
• step 10:
• in an organic solvent and water, adding a base to the compound of formula 8 for hydrolysis to give a compound of formula 9;
• step 11:
• in a solvent, in the presence of a base, subjecting the carboxylic acid compound of formula 9 to an acylation reaction with pivaloyl chloride to give an anhydride compound of formula 24;
• step 12:
• in an organic solvent and water, in the presence of a base, subjecting a compound of formula 13 to an imidization reaction as shown with a compound of formula 14 to give a guanidine compound of formula 15;
• step 13:
• in a solvent, in the presence of triphenylphosphine, imidazole and iodine, subjecting the guanidine compound of formula 15 to an Appel reaction and a ring-closing reaction as shown to give an azacycle compound of formula 16 and/or a tautomer thereof;
• step 14:
• subjecting a hydrazine to a hydrazidation reaction as shown with the azacycle compound of formula 16 and/or the tautomer thereof to give a hydrazide compound of formula 17 and/or a tautomer thereof;
• step 15:
• subjecting the anhydride compound of formula 24 to an amidation reaction with the hydrazine compound of formula 17 and/or the tautomer thereof to give a hydrazide compound of formula 18 and/or a tautomer thereof;
• step 16:
• in a solvent, in the presence of a dehydrating agent and a base, subjecting the hydrazide compound of formula 18 and/or the tautomer thereof to a ring-closing reaction as shown to give an oxadiazazole compound of formula 19 and/or a tautomer thereof;
• step 17:
• in an organic solvent and water, under an acidic condition, subjecting the hydrazide compound of formula 19 to a tautomerization reaction as shown to give a tautomer thereof, namely an oxadiazazole compound of formula 20;
• step 18:
• in a solvent, in the presence of a palladium catalyst and hydrogen, subjecting the imidazoline compound of formula 20 and/or a tautomer thereof to a debenzylation reaction as shown to give a hydroxylamine compound of formula 21 and/or a tautomer thereof;
• step 19:
• in a solvent, in the presence of pyridine and a sulfonation reagent, subjecting the hydroxylamine compound of formula 21 and/or the tautomer thereof to a sulfonation reaction as shown to give a sulfonic acid oxygen compound of formula 22 and/or a tautomer thereof;
• and
• step 20:
• in water and an organic solvent, subjecting the sulfonic acid oxygen compound of formula 22 and/or the tautomer thereof to an amine protecting group-removing reaction as shown to give an imine compound of formula I.