1192491-61-4

Basic information

• Product Name: NXL 104
• Synonyms: AvibactaM SodiuM Salt;NXL 104;Sulfuric Acid Mono[(1R,2S,5R)-2-(aMinocarbonyl)-7-oxo-1,6-diazabicyclo[3.2.1]oct-6-yl] Ester SodiuM Salt;Avibactam (sodium);AvibactaM SodiuM NXL 104;sodium (1R,2S,5R)-2-carbamoyl-7-oxo-1,6-diazabicyclo[3.2.1]octan-6-yl sulfate;(2S,5R)-7-Oxo-6-(sulfooxy)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide monosodium salt;(2S,5R)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide 7-oxo-6-(sulfoxy)monosodium salt
• CAS NO: 1192491-61-4
• Molecular Formula: C₇H₁₀N₃O₆S*Na
• Molecular Weight: 287.22557
• Product Categories: Amines;Chiral Reagents;Intermediates & Fine Chemicals;Pharmaceuticals;Sulfur & Selenium Compounds;Amines, Chiral Reagents, Pharmaceuticals, Intermediates & Fine Chemicals, Sulfur & Selenium Compounds;API
• Mol File: 1192491-61-4.mol
• Article Data: 27

Chemical Properties

• Appearance: /
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: DMSO (Slightly), Methanol (Slightly, Heated, Sonicated), Water (Slightly, Sonica
• CAS DataBase Reference: NXL 104(CAS DataBase Reference)
• NIST Chemistry Reference: NXL 104(1192491-61-4)
• EPA Substance Registry System: NXL 104(1192491-61-4)

Safety Data

• Hazardous Substances Data: 1192491-61-4(Hazardous Substances Data)

Usage

Description

Avibactam is a β-lactamase inhibitor (IC50s = 8, 80, and 38 nM for TEM-1, P99, and KPC-2 β-lactamases, respectively). It restores the antimicrobial activity of ceftazidime , ceftriaxone , imipenem , and piperacillin against antibiotic-resistant Enterobacteriaceae in vitro (MIC90 reduction 4-1,024-fold across 190 E. coli and K. pneumoniae clinical isolates). Formulations containing avibactam have been used to treat carbapenem-resistant Enterobacteriaceae infections.

Uses

Avibactam (NXL104) is a novel β-lactamase inhibitor with a non-lactam structural scaffold. NXL104 irreversibly inhibits lactamase from Mycobacterium tuberculosis.

Definition

ChEBI: An organic sodium salt that is the monosodium salt of avibactam. Used in combination with ceftazidime pentahydrate for the treatment of complicated urinary tract infections including pyelonephritis.

Synthetic route

({[(2S,5R)-2-carbamoyl-7-oxo-6-(sulfooxy)-1,6-diazabicyclo[3,2,1]-oct-6-yl]oxy}sulfonyl)tetrabutylammonium salt (1192651-80-1, 1416134-53-6) → (2S,5R)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide 7-oxo-6-(sulfoxy)monosodium salt (1192491-61-4)

Conditions	Yield
Stage #1: ({[(2S,5R)-2-carbamoyl-7-oxo-6-(sulfooxy)-1,6-diazabicyclo[3,2,1]-oct-6-yl]oxy}sulfonyl)tetrabutylammonium salt With tetrafluoroboric acid; 2,2,2-trifluoroethanol Stage #2: With sodium hydrogencarbonate at 0℃; for 1h;	100%
With sodium 2-ethylhexanoic acid In ethanol; water at 20℃; for 3h;	99.6%
With sodium 2-ethylhexanoic acid In ethanol; water at 20℃; for 3h;	96.2%

2C7H10N3O6S(1-)*C30H66N2(2+) → (2S,5R)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide 7-oxo-6-(sulfoxy)monosodium salt (1192491-61-4)

Conditions	Yield
With sodium 2-ethylhexanoic acid In ethanol	89%

C7H10N3O6S(1-)*C16H34N(1+) → (2S,5R)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide 7-oxo-6-(sulfoxy)monosodium salt (1192491-61-4)

Conditions	Yield
With sodium 2-ethylhexanoic acid In ethanol	88%

C7H10N3O6S(1-)*C14H30N(1+) → (2S,5R)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide 7-oxo-6-(sulfoxy)monosodium salt (1192491-61-4)

Conditions	Yield
With sodium 2-ethylhexanoic acid In ethanol	86%

2C7H10N3O6S(1-)*C38H66N2(2+) → (2S,5R)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide 7-oxo-6-(sulfoxy)monosodium salt (1192491-61-4)

Conditions	Yield
With sodium 2-ethylhexanoic acid In ethanol	86%

2C7H10N3O6S(1-)*C29H64N2(2+) → (2S,5R)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide 7-oxo-6-(sulfoxy)monosodium salt (1192491-61-4)

Conditions	Yield
With sodium 2-ethylhexanoic acid In ethanol	86%

(2S,5R)-6-hydroxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamide → (2S,5R)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide 7-oxo-6-(sulfoxy)monosodium salt (1192491-61-4)

Conditions	Yield
Stage #1: (2S,5R)-6-hydroxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamide With pyridine; sulfur trioxide pyridine complex at 20℃; for 20h; Stage #2: With sodium dihydrogenphosphate In water	80%
Multi-step reaction with 2 steps 1.1: α-picoline; thiocyanate trioxide / tetrahydrofuran / 24 h / 20 °C / Inert atmosphere 2.1: 2,2,2-trifluoroethanol; tetrafluoroboric acid 2.2: 1 h / 0 °C View Scheme
Multi-step reaction with 2 steps 1: triethylamine; sulfur trioxide trimethylamine complex / ethanol; water 2: sodium 2-ethylhexanoic acid / ethanol View Scheme
Multi-step reaction with 2 steps 1: triethylamine; sulfur trioxide trimethylamine complex / ethanol; water 2: sodium 2-ethylhexanoic acid / ethanol View Scheme
Multi-step reaction with 3 steps 1.1: sodium hexamethyldisilazane; 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone / tetrahydrofuran / 0.17 h / -78 °C / Inert atmosphere 1.2: -78 - 20 °C / Inert atmosphere 2.1: palladium 10% on activated carbon; hydrogen / acetonitrile / 1.33 h / 20 °C / Inert atmosphere 3.1: sodium hydrogencarbonate / dimethylsulfoxide-d6; water-d2 View Scheme

(1R,2S,5R)-7-oxo-6-sulfonyloxy-1,6-diazabicyclo[3,2,1]octane-2-carboxamide tributylbenzylammonium → (2S,5R)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide 7-oxo-6-(sulfoxy)monosodium salt (1192491-61-4)

Conditions	Yield
With sodium 2-ethylhexanoic acid In ethanol; water at 15 - 40℃; for 4h;	80%
With sodium 2-ethylhexanoic acid In ethanol	4.6 g
With sodium isooctanoate In ethanol; water at 35 - 40℃; for 4h;

2C7H10N3O6S(1-)*C28H62N2(2+) → (2S,5R)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide 7-oxo-6-(sulfoxy)monosodium salt (1192491-61-4)

Conditions	Yield
With sodium 2-ethylhexanoic acid In ethanol	80%

(2S,5R)-2-carbamoyl-7-oxo-1,6-diazabicylco[3.2.1]octan-6-yl hydrogensulfate (1192500-31-4) + sodium 2-ethylhexanoic acid → (2S,5R)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide 7-oxo-6-(sulfoxy)monosodium salt (1192491-61-4)

Conditions	Yield
In 2-methyl-propan-1-ol for 0.833333h; Solvent; Time; Concentration; Reflux;	77%

2C7H10N3O6S(1-)*C23H52N2(2+) → (2S,5R)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide 7-oxo-6-(sulfoxy)monosodium salt (1192491-61-4)

Conditions	Yield
With sodium 2-ethylhexanoic acid In ethanol	74%

2C7H10N3O6S(1-)*C32H54N2(2+) → (2S,5R)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide 7-oxo-6-(sulfoxy)monosodium salt (1192491-61-4)

Conditions	Yield
With sodium 2-ethylhexanoic acid In ethanol	74%

(1R,2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxamide (1192651-49-2) → (2S,5R)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide 7-oxo-6-(sulfoxy)monosodium salt (1192491-61-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: triethylamine; hydrogen; sulfur trioxide trimethylamine complex / palladium-on-charcoal / isopropyl alcohol; water 2: sodium 2-ethylhexanoic acid / ethanol; water View Scheme
Multi-step reaction with 3 steps 1.1: hydrogen / 5% Pd-C / dichloromethane; N,N-dimethyl-formamide 1.2: 20 °C 1.3: pH > 6 2.1: dichloromethane; water 3.1: sodium 2-ethylhexanoic acid / ethanol; water View Scheme
Multi-step reaction with 3 steps 1: hydrogen / 5% Pd-C / dichloromethane; N,N-dimethyl-formamide / 2250.23 Torr 2: water 3: sodium 2-ethylhexanoic acid / ethanol; water View Scheme

(2S,5R)-5-(benzyloxyamino)-piperidine-2-carboxylic acid amide (1416134-49-0) → (2S,5R)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide 7-oxo-6-(sulfoxy)monosodium salt (1192491-61-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: N-ethyl-N,N-diisopropylamine; (fluorenylmethoxy)carbonyl chloride / chlorobenzene / 30 °C 2: triethylamine; hydrogen; sulfur trioxide trimethylamine complex / palladium-on-charcoal / isopropyl alcohol; water 3: sodium 2-ethylhexanoic acid / ethanol; water View Scheme
Multi-step reaction with 4 steps 1.1: N-ethyl-N,N-diisopropylamine; (fluorenylmethoxy)carbonyl chloride / chlorobenzene / 30 °C 2.1: hydrogen / 5% Pd-C / dichloromethane; N,N-dimethyl-formamide 2.2: 20 °C 2.3: pH > 6 3.1: dichloromethane; water 4.1: sodium 2-ethylhexanoic acid / ethanol; water View Scheme
Multi-step reaction with 4 steps 1: N-ethyl-N,N-diisopropylamine; (fluorenylmethoxy)carbonyl chloride / chlorobenzene / 30 °C 2: hydrogen / 5% Pd-C / dichloromethane; N,N-dimethyl-formamide / 2250.23 Torr 3: water 4: sodium 2-ethylhexanoic acid / ethanol; water View Scheme

(2S,5R)-5-benzyloxyaminopiperidin-2-carboxylic acid benzyl ester oxalic acid salt (1171080-45-7) → (2S,5R)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide 7-oxo-6-(sulfoxy)monosodium salt (1192491-61-4)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: potassium hydrogencarbonate / water; 2-methyltetrahydrofuran 1.2: 0 °C 2.1: water; lithium hydroxide monohydrate / acetone / -12 °C 2.2: 0 °C 2.3: -20 - 0 °C 3.1: triethylamine; hydrogen; sulfur trioxide trimethylamine complex / palladium-on-charcoal / isopropyl alcohol; water 4.1: sodium 2-ethylhexanoic acid / ethanol; water View Scheme
Multi-step reaction with 4 steps 1: ammonia / methanol 2: N-ethyl-N,N-diisopropylamine; (fluorenylmethoxy)carbonyl chloride / chlorobenzene / 30 °C 3: triethylamine; hydrogen; sulfur trioxide trimethylamine complex / palladium-on-charcoal / isopropyl alcohol; water 4: sodium 2-ethylhexanoic acid / ethanol; water View Scheme
Multi-step reaction with 5 steps 1.1: potassium hydrogencarbonate / water; 2-methyltetrahydrofuran 1.2: 0 °C 2.1: water; lithium hydroxide monohydrate / acetone / -12 °C 2.2: 0 °C 2.3: -20 - 0 °C 3.1: hydrogen / 5% Pd-C / dichloromethane; N,N-dimethyl-formamide / 2250.23 Torr 4.1: water 5.1: sodium 2-ethylhexanoic acid / ethanol; water View Scheme

ethyl (2S,5R)-5-[(benzyloxy)amino]piperidine-2-carboxylate oxalic acid salt (1416134-48-9) → (2S,5R)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide 7-oxo-6-(sulfoxy)monosodium salt (1192491-61-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: 3-Methylpyridine / dichloromethane / 0 °C 2: ammonium carbamate / Novozyme 435 / dichloromethane; acetonitrile / 40 °C / Enzymatic reaction 3: triethylamine; hydrogen; sulfur trioxide trimethylamine complex / palladium-on-charcoal / isopropyl alcohol; water 4: sodium 2-ethylhexanoic acid / ethanol; water View Scheme
Multi-step reaction with 4 steps 1: ammonia / methanol / 20 °C 2: N-ethyl-N,N-diisopropylamine; (fluorenylmethoxy)carbonyl chloride / chlorobenzene / 30 °C 3: triethylamine; hydrogen; sulfur trioxide trimethylamine complex / palladium-on-charcoal / isopropyl alcohol; water 4: sodium 2-ethylhexanoic acid / ethanol; water View Scheme
Multi-step reaction with 5 steps 1.1: 3-Methylpyridine / dichloromethane / 0 °C 2.1: ammonium carbamate / Novozyme 435 / dichloromethane; acetonitrile / 40 °C / Enzymatic reaction 3.1: hydrogen / 5% Pd-C / dichloromethane; N,N-dimethyl-formamide 3.2: 20 °C 3.3: pH > 6 4.1: dichloromethane; water 5.1: sodium 2-ethylhexanoic acid / ethanol; water View Scheme

benzyl (2S)-N-tert-butoxycarbonyl-5-oxoprolinate (113400-36-5) → (2S,5R)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide 7-oxo-6-(sulfoxy)monosodium salt (1192491-61-4)

Conditions	Yield
Multi-step reaction with 10 steps 1.1: potassium tert-butylate / dimethyl sulfoxide; tetrahydrofuran / 20 °C 1.2: -12 °C 2.1: ethyl acetate / Reflux 3.1: methanesulfonic acid / ethyl acetate / 42 °C 3.2: 52 °C 4.1: sodium tetrahydroborate; sulfuric acid; propionic acid / ethyl acetate / -20 °C 4.3: 40 - 45 °C 5.1: 1 h / 0 °C 5.2: 35 °C 6.1: ammonia / methanol / 20 °C 7.1: N-ethyl-N,N-diisopropylamine; (fluorenylmethoxy)carbonyl chloride / chlorobenzene / 30 °C 8.1: hydrogen / 5% Pd-C / dichloromethane; N,N-dimethyl-formamide / 2250.23 Torr 9.1: water 10.1: sodium 2-ethylhexanoic acid / ethanol; water View Scheme
Multi-step reaction with 10 steps 1.1: potassium tert-butylate / dimethyl sulfoxide; tetrahydrofuran / 20 °C 1.2: -12 °C 2.1: ethyl acetate / Reflux 3.1: methanesulfonic acid / ethyl acetate / 42 °C 3.2: 52 °C 4.1: sodium tetrahydroborate; sulfuric acid; propionic acid / ethyl acetate / -20 °C 4.3: 40 - 45 °C 5.1: 1 h / 0 °C 5.2: 35 °C 6.1: ammonia / methanol / 20 °C 7.1: N-ethyl-N,N-diisopropylamine; (fluorenylmethoxy)carbonyl chloride / chlorobenzene / 30 °C 8.1: hydrogen / 5% Pd-C / dichloromethane; N,N-dimethyl-formamide 8.2: 20 °C 8.3: pH > 6 9.1: dichloromethane; water 10.1: sodium 2-ethylhexanoic acid / ethanol; water View Scheme
Multi-step reaction with 8 steps 1.1: potassium tert-butylate / dimethyl sulfoxide; tetrahydrofuran / 20 °C 1.2: -12 °C 2.1: ethyl acetate / Reflux 3.1: methanesulfonic acid / ethyl acetate / 42 °C 3.2: 52 °C 4.1: sodium tetrahydroborate; sulfuric acid; propionic acid / ethyl acetate / -20 °C 4.3: 40 - 45 °C 5.1: ammonia / methanol 6.1: N-ethyl-N,N-diisopropylamine; (fluorenylmethoxy)carbonyl chloride / chlorobenzene / 30 °C 7.1: triethylamine; hydrogen; sulfur trioxide trimethylamine complex / palladium-on-charcoal / isopropyl alcohol; water 8.1: sodium 2-ethylhexanoic acid / ethanol; water View Scheme

(S)-ethyl N-tert-butoxycarbonylpyroglutamate (144978-35-8, 144978-12-1) → (2S,5R)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide 7-oxo-6-(sulfoxy)monosodium salt (1192491-61-4)

Conditions	Yield
Multi-step reaction with 8 steps 1.1: potassium tert-butylate / dimethyl sulfoxide; tetrahydrofuran / 20 °C 1.2: -12 °C 2.1: ethyl acetate / Reflux 3.1: methanesulfonic acid / ethyl acetate / 42 °C 3.2: 52 °C 4.1: sodium tetrahydroborate; sulfuric acid; propionic acid / ethyl acetate / -20 °C 4.3: 40 - 45 °C 5.1: ammonia / methanol / 20 °C 6.1: N-ethyl-N,N-diisopropylamine; (fluorenylmethoxy)carbonyl chloride / chlorobenzene / 30 °C 7.1: triethylamine; hydrogen; sulfur trioxide trimethylamine complex / palladium-on-charcoal / isopropyl alcohol; water 8.1: sodium 2-ethylhexanoic acid / ethanol; water View Scheme
Multi-step reaction with 9 steps 1.1: potassium tert-butylate / dimethyl sulfoxide; tetrahydrofuran / 20 °C 1.2: -12 °C 2.1: ethyl acetate / Reflux 3.1: methanesulfonic acid / ethyl acetate / 42 °C 3.2: 52 °C 4.1: sodium tetrahydroborate; sulfuric acid; propionic acid / ethyl acetate / -20 °C 4.3: 40 - 45 °C 5.1: ammonia / methanol / 20 °C 6.1: N-ethyl-N,N-diisopropylamine; (fluorenylmethoxy)carbonyl chloride / chlorobenzene / 30 °C 7.1: hydrogen / 5% Pd-C / dichloromethane; N,N-dimethyl-formamide / 2250.23 Torr 8.1: water 9.1: sodium 2-ethylhexanoic acid / ethanol; water View Scheme
Multi-step reaction with 9 steps 1.1: potassium tert-butylate / dimethyl sulfoxide; tetrahydrofuran / 20 °C 1.2: -12 °C 2.1: ethyl acetate / Reflux 3.1: methanesulfonic acid / ethyl acetate / 42 °C 3.2: 52 °C 4.1: sodium tetrahydroborate; sulfuric acid; propionic acid / ethyl acetate / -20 °C 4.3: 40 - 45 °C 5.1: ammonia / methanol / 20 °C 6.1: N-ethyl-N,N-diisopropylamine; (fluorenylmethoxy)carbonyl chloride / chlorobenzene / 30 °C 7.1: hydrogen / 5% Pd-C / dichloromethane; N,N-dimethyl-formamide 7.2: 20 °C 7.3: pH > 6 8.1: dichloromethane; water 9.1: sodium 2-ethylhexanoic acid / ethanol; water View Scheme

benzyl (2S)-2-((tert-butoxycarbonyl)amino)-6-(dimethyl(oxo)-λ6-sulfanylidene)-5-oxohexanoate → (2S,5R)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide 7-oxo-6-(sulfoxy)monosodium salt (1192491-61-4)

Conditions	Yield
Multi-step reaction with 7 steps 1.1: ethyl acetate / Reflux 2.1: methanesulfonic acid / ethyl acetate / 42 °C 2.2: 52 °C 3.1: sodium tetrahydroborate; sulfuric acid; propionic acid / ethyl acetate / -20 °C 3.3: 40 - 45 °C 4.1: ammonia / methanol 5.1: N-ethyl-N,N-diisopropylamine; (fluorenylmethoxy)carbonyl chloride / chlorobenzene / 30 °C 6.1: triethylamine; hydrogen; sulfur trioxide trimethylamine complex / palladium-on-charcoal / isopropyl alcohol; water 7.1: sodium 2-ethylhexanoic acid / ethanol; water View Scheme
Multi-step reaction with 7 steps 1.1: ethyl acetate / Reflux 2.1: methanesulfonic acid / ethyl acetate / 42 °C 2.2: 52 °C 3.1: sodium tetrahydroborate; sulfuric acid; propionic acid / ethyl acetate / -20 °C 3.3: 40 - 45 °C 4.1: potassium hydrogencarbonate / water; 2-methyltetrahydrofuran 4.2: 0 °C 5.1: water; lithium hydroxide monohydrate / acetone / -12 °C 5.2: 0 °C 5.3: -20 - 0 °C 6.1: triethylamine; hydrogen; sulfur trioxide trimethylamine complex / palladium-on-charcoal / isopropyl alcohol; water 7.1: sodium 2-ethylhexanoic acid / ethanol; water View Scheme
Multi-step reaction with 8 steps 1.1: ethyl acetate / Reflux 2.1: methanesulfonic acid / ethyl acetate / 42 °C 2.2: 52 °C 3.1: sodium tetrahydroborate; sulfuric acid; propionic acid / ethyl acetate / -20 °C 3.3: 40 - 45 °C 4.1: 1 h / 0 °C 4.2: 35 °C 5.1: ammonia / methanol / 20 °C 6.1: N-ethyl-N,N-diisopropylamine; (fluorenylmethoxy)carbonyl chloride / chlorobenzene / 30 °C 7.1: triethylamine; hydrogen; sulfur trioxide trimethylamine complex / palladium-on-charcoal / isopropyl alcohol; water 8.1: sodium 2-ethylhexanoic acid / ethanol; water View Scheme

(2S)-5-(benzyloxyimino)-piperidine-2-carboxylic acid benzyl ester (1133931-74-4) → (2S,5R)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide 7-oxo-6-(sulfoxy)monosodium salt (1192491-61-4)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: sodium tetrahydroborate; sulfuric acid; propionic acid / ethyl acetate / -20 °C 1.3: 40 - 45 °C 2.1: ammonia / methanol 3.1: N-ethyl-N,N-diisopropylamine; (fluorenylmethoxy)carbonyl chloride / chlorobenzene / 30 °C 4.1: triethylamine; hydrogen; sulfur trioxide trimethylamine complex / palladium-on-charcoal / isopropyl alcohol; water 5.1: sodium 2-ethylhexanoic acid / ethanol; water View Scheme
Multi-step reaction with 5 steps 1.1: sodium tetrahydroborate; sulfuric acid; propionic acid / ethyl acetate / -20 °C 1.3: 40 - 45 °C 2.1: potassium hydrogencarbonate / water; 2-methyltetrahydrofuran 2.2: 0 °C 3.1: water; lithium hydroxide monohydrate / acetone / -12 °C 3.2: 0 °C 3.3: -20 - 0 °C 4.1: triethylamine; hydrogen; sulfur trioxide trimethylamine complex / palladium-on-charcoal / isopropyl alcohol; water 5.1: sodium 2-ethylhexanoic acid / ethanol; water View Scheme
Multi-step reaction with 6 steps 1.1: sodium tetrahydroborate; sulfuric acid; propionic acid / ethyl acetate / -20 °C 1.3: 40 - 45 °C 2.1: ammonia / methanol 3.1: N-ethyl-N,N-diisopropylamine; (fluorenylmethoxy)carbonyl chloride / chlorobenzene / 30 °C 4.1: hydrogen / 5% Pd-C / dichloromethane; N,N-dimethyl-formamide / 2250.23 Torr 5.1: water 6.1: sodium 2-ethylhexanoic acid / ethanol; water View Scheme

(2S)-5-benzyloxyaminopiperidin-2-carboxylic acid benzyl ester oxalic acid salt → (2S,5R)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide 7-oxo-6-(sulfoxy)monosodium salt (1192491-61-4)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: methanol / 25 °C / Reflux 2.1: potassium hydrogencarbonate / water; 2-methyltetrahydrofuran 2.2: 0 °C 3.1: water; lithium hydroxide monohydrate / acetone / -12 °C 3.2: 0 °C 3.3: -20 - 0 °C 4.1: triethylamine; hydrogen; sulfur trioxide trimethylamine complex / palladium-on-charcoal / isopropyl alcohol; water 5.1: sodium 2-ethylhexanoic acid / ethanol; water View Scheme
Multi-step reaction with 5 steps 1: methanol / 25 °C / Reflux 2: ammonia / methanol 3: N-ethyl-N,N-diisopropylamine; (fluorenylmethoxy)carbonyl chloride / chlorobenzene / 30 °C 4: triethylamine; hydrogen; sulfur trioxide trimethylamine complex / palladium-on-charcoal / isopropyl alcohol; water 5: sodium 2-ethylhexanoic acid / ethanol; water View Scheme
Multi-step reaction with 6 steps 1.1: methanol / 25 °C / Reflux 2.1: potassium hydrogencarbonate / water; 2-methyltetrahydrofuran 2.2: 0 °C 3.1: water; lithium hydroxide monohydrate / acetone / -12 °C 3.2: 0 °C 3.3: -20 - 0 °C 4.1: hydrogen / 5% Pd-C / dichloromethane; N,N-dimethyl-formamide / 2250.23 Torr 5.1: water 6.1: sodium 2-ethylhexanoic acid / ethanol; water View Scheme

benzyl (2S)-5-[(benzyloxy)imino]-2-{[(tert-butoxy)carbonyl]amino}-6-chlorohexanoate (1133931-73-3) → (2S,5R)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide 7-oxo-6-(sulfoxy)monosodium salt (1192491-61-4)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: methanesulfonic acid / ethyl acetate / 42 °C 1.2: 52 °C 2.1: sodium tetrahydroborate; sulfuric acid; propionic acid / ethyl acetate / -20 °C 2.3: 40 - 45 °C 3.1: ammonia / methanol 4.1: N-ethyl-N,N-diisopropylamine; (fluorenylmethoxy)carbonyl chloride / chlorobenzene / 30 °C 5.1: triethylamine; hydrogen; sulfur trioxide trimethylamine complex / palladium-on-charcoal / isopropyl alcohol; water 6.1: sodium 2-ethylhexanoic acid / ethanol; water View Scheme
Multi-step reaction with 6 steps 1.1: methanesulfonic acid / ethyl acetate / 42 °C 1.2: 52 °C 2.1: sodium tetrahydroborate; sulfuric acid; propionic acid / ethyl acetate / -20 °C 2.3: 40 - 45 °C 3.1: potassium hydrogencarbonate / water; 2-methyltetrahydrofuran 3.2: 0 °C 4.1: water; lithium hydroxide monohydrate / acetone / -12 °C 4.2: 0 °C 4.3: -20 - 0 °C 5.1: triethylamine; hydrogen; sulfur trioxide trimethylamine complex / palladium-on-charcoal / isopropyl alcohol; water 6.1: sodium 2-ethylhexanoic acid / ethanol; water View Scheme
Multi-step reaction with 7 steps 1.1: methanesulfonic acid / ethyl acetate / 42 °C 1.2: 52 °C 2.1: sodium tetrahydroborate; sulfuric acid; propionic acid / ethyl acetate / -20 °C 2.3: 40 - 45 °C 3.1: 1 h / 0 °C 3.2: 35 °C 4.1: ammonia / methanol / 20 °C 5.1: N-ethyl-N,N-diisopropylamine; (fluorenylmethoxy)carbonyl chloride / chlorobenzene / 30 °C 6.1: triethylamine; hydrogen; sulfur trioxide trimethylamine complex / palladium-on-charcoal / isopropyl alcohol; water 7.1: sodium 2-ethylhexanoic acid / ethanol; water View Scheme

(2S,5R)-6-benzyloxy-7-oxo-1,6-diazabicyclo[3.2.1]octan-2-carboxylic acid methyl ester (1383814-58-1) → (2S,5R)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide 7-oxo-6-(sulfoxy)monosodium salt (1192491-61-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: ammonium carbamate / Novozyme 435 / acetonitrile / 40 °C / Enzymatic reaction 2: triethylamine; hydrogen; sulfur trioxide trimethylamine complex / palladium-on-charcoal / isopropyl alcohol; water 3: sodium 2-ethylhexanoic acid / ethanol; water View Scheme
Multi-step reaction with 4 steps 1.1: ammonium carbamate / Novozyme 435 / acetonitrile / 40 °C / Enzymatic reaction 2.1: hydrogen / 5% Pd-C / dichloromethane; N,N-dimethyl-formamide 2.2: 20 °C 2.3: pH > 6 3.1: dichloromethane; water 4.1: sodium 2-ethylhexanoic acid / ethanol; water View Scheme
Multi-step reaction with 4 steps 1: ammonium carbamate / Novozyme 435 / acetonitrile / 40 °C / Enzymatic reaction 2: hydrogen / 5% Pd-C / dichloromethane; N,N-dimethyl-formamide / 2250.23 Torr 3: water 4: sodium 2-ethylhexanoic acid / ethanol; water View Scheme
Multi-step reaction with 4 steps 1.1: lithium hydroxide monohydrate / water; tetrahydrofuran / 0.25 h / 0 °C 2.1: triethylamine; isobutyl chloroformate / dichloromethane / 0.33 h / 0 °C 2.2: 1 h / 20 °C 3.1: hydrogen; palladium 10% on activated carbon / water; methanol / 0.75 h 4.1: pyridine; sulfur trioxide pyridine complex / 20 h / 20 °C View Scheme
Multi-step reaction with 5 steps 1.1: lithium hydroxide monohydrate / water; tetrahydrofuran / 0.25 h / 0 °C 2.1: 4-methyl-morpholine; isobutyl chloroformate / dichloromethane / 0.17 h / 0 °C 2.2: 0.5 h 3.1: ammonium hydroxide / dichloromethane / 1 h / 0 - 20 °C 4.1: hydrogen; palladium 10% on activated carbon / water; methanol / 0.75 h 5.1: pyridine; sulfur trioxide pyridine complex / 20 h / 20 °C View Scheme

(2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octan-2-carboxylic acid benzyl ester (1192650-82-0) → (2S,5R)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide 7-oxo-6-(sulfoxy)monosodium salt (1192491-61-4)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: water; lithium hydroxide monohydrate / acetone / -12 °C 1.2: 0 °C 1.3: -20 - 0 °C 2.1: triethylamine; hydrogen; sulfur trioxide trimethylamine complex / palladium-on-charcoal / isopropyl alcohol; water 3.1: sodium 2-ethylhexanoic acid / ethanol; water View Scheme
Multi-step reaction with 4 steps 1.1: water; lithium hydroxide monohydrate / acetone / -12 °C 1.2: 0 °C 1.3: -20 - 0 °C 2.1: hydrogen / 5% Pd-C / dichloromethane; N,N-dimethyl-formamide / 2250.23 Torr 3.1: water 4.1: sodium 2-ethylhexanoic acid / ethanol; water View Scheme
Multi-step reaction with 4 steps 1.1: water; lithium hydroxide monohydrate / acetone / -12 °C 1.2: 0 °C 1.3: -20 - 0 °C 2.1: hydrogen / 5% Pd-C / dichloromethane; N,N-dimethyl-formamide 2.2: 20 °C 2.3: pH > 6 3.1: dichloromethane; water 4.1: sodium 2-ethylhexanoic acid / ethanol; water View Scheme

methyl (2S,5R)-5-benzyloxyaminopiperidine-2-carboxylate oxalate (1416134-74-1) → (2S,5R)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide 7-oxo-6-(sulfoxy)monosodium salt (1192491-61-4)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: potassium hydrogencarbonate / water; 2-methyltetrahydrofuran 1.2: -5 - -3 °C 2.1: ammonium carbamate / Novozyme 435 / acetonitrile / 40 °C / Enzymatic reaction 3.1: triethylamine; hydrogen; sulfur trioxide trimethylamine complex / palladium-on-charcoal / isopropyl alcohol; water 4.1: sodium 2-ethylhexanoic acid / ethanol; water View Scheme
Multi-step reaction with 4 steps 1: ammonia / methanol / 20 °C 2: N-ethyl-N,N-diisopropylamine; (fluorenylmethoxy)carbonyl chloride / chlorobenzene / 30 °C 3: triethylamine; hydrogen; sulfur trioxide trimethylamine complex / palladium-on-charcoal / isopropyl alcohol; water 4: sodium 2-ethylhexanoic acid / ethanol; water View Scheme
Multi-step reaction with 5 steps 1.1: potassium hydrogencarbonate / water; 2-methyltetrahydrofuran 1.2: -5 - -3 °C 2.1: ammonium carbamate / Novozyme 435 / acetonitrile / 40 °C / Enzymatic reaction 3.1: hydrogen / 5% Pd-C / dichloromethane; N,N-dimethyl-formamide / 2250.23 Torr 4.1: water 5.1: sodium 2-ethylhexanoic acid / ethanol; water View Scheme

ethyl (S)-2-((tert-butoxycarbonyl)amino)-6-(dimethyl(oxo)-λ6-sulfanylidene)-5-oxohexanoate (1416134-58-1) → (2S,5R)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide 7-oxo-6-(sulfoxy)monosodium salt (1192491-61-4)

Conditions	Yield
Multi-step reaction with 7 steps 1.1: ethyl acetate / Reflux 2.1: methanesulfonic acid / ethyl acetate / 42 °C 2.2: 52 °C 3.1: sodium tetrahydroborate; sulfuric acid; propionic acid / ethyl acetate / -20 °C 3.3: 40 - 45 °C 4.1: ammonia / methanol / 20 °C 5.1: N-ethyl-N,N-diisopropylamine; (fluorenylmethoxy)carbonyl chloride / chlorobenzene / 30 °C 6.1: triethylamine; hydrogen; sulfur trioxide trimethylamine complex / palladium-on-charcoal / isopropyl alcohol; water 7.1: sodium 2-ethylhexanoic acid / ethanol; water View Scheme
Multi-step reaction with 7 steps 1.1: ethyl acetate / Reflux 2.1: methanesulfonic acid / ethyl acetate / 42 °C 2.2: 52 °C 3.1: sodium tetrahydroborate; sulfuric acid; propionic acid / ethyl acetate / -20 °C 3.3: 40 - 45 °C 4.1: 3-Methylpyridine / dichloromethane / 0 °C 5.1: ammonium carbamate / Novozyme 435 / dichloromethane; acetonitrile / 40 °C / Enzymatic reaction 6.1: triethylamine; hydrogen; sulfur trioxide trimethylamine complex / palladium-on-charcoal / isopropyl alcohol; water 7.1: sodium 2-ethylhexanoic acid / ethanol; water View Scheme
Multi-step reaction with 8 steps 1.1: ethyl acetate / Reflux 2.1: methanesulfonic acid / ethyl acetate / 42 °C 2.2: 52 °C 3.1: sodium tetrahydroborate; sulfuric acid; propionic acid / ethyl acetate / -20 °C 3.3: 40 - 45 °C 4.1: ammonia / methanol / 20 °C 5.1: N-ethyl-N,N-diisopropylamine; (fluorenylmethoxy)carbonyl chloride / chlorobenzene / 30 °C 6.1: hydrogen / 5% Pd-C / dichloromethane; N,N-dimethyl-formamide / 2250.23 Torr 7.1: water 8.1: sodium 2-ethylhexanoic acid / ethanol; water View Scheme

C20H29ClN2O5 (1416134-59-2) → (2S,5R)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide 7-oxo-6-(sulfoxy)monosodium salt (1192491-61-4)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: methanesulfonic acid / ethyl acetate / 42 °C 1.2: 52 °C 2.1: sodium tetrahydroborate; sulfuric acid; propionic acid / ethyl acetate / -20 °C 2.3: 40 - 45 °C 3.1: ammonia / methanol / 20 °C 4.1: N-ethyl-N,N-diisopropylamine; (fluorenylmethoxy)carbonyl chloride / chlorobenzene / 30 °C 5.1: triethylamine; hydrogen; sulfur trioxide trimethylamine complex / palladium-on-charcoal / isopropyl alcohol; water 6.1: sodium 2-ethylhexanoic acid / ethanol; water View Scheme
Multi-step reaction with 6 steps 1.1: methanesulfonic acid / ethyl acetate / 42 °C 1.2: 52 °C 2.1: sodium tetrahydroborate; sulfuric acid; propionic acid / ethyl acetate / -20 °C 2.3: 40 - 45 °C 3.1: 3-Methylpyridine / dichloromethane / 0 °C 4.1: ammonium carbamate / Novozyme 435 / dichloromethane; acetonitrile / 40 °C / Enzymatic reaction 5.1: triethylamine; hydrogen; sulfur trioxide trimethylamine complex / palladium-on-charcoal / isopropyl alcohol; water 6.1: sodium 2-ethylhexanoic acid / ethanol; water View Scheme
Multi-step reaction with 7 steps 1.1: methanesulfonic acid / ethyl acetate / 42 °C 1.2: 52 °C 2.1: sodium tetrahydroborate; sulfuric acid; propionic acid / ethyl acetate / -20 °C 2.3: 40 - 45 °C 3.1: ammonia / methanol / 20 °C 4.1: N-ethyl-N,N-diisopropylamine; (fluorenylmethoxy)carbonyl chloride / chlorobenzene / 30 °C 5.1: hydrogen / 5% Pd-C / dichloromethane; N,N-dimethyl-formamide / 2250.23 Torr 6.1: water 7.1: sodium 2-ethylhexanoic acid / ethanol; water View Scheme

5-benzyloxyiminopiperidine-2S-carboxylic acid ethyl ester (1416134-60-5) → (2S,5R)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide 7-oxo-6-(sulfoxy)monosodium salt (1192491-61-4)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: sodium tetrahydroborate; sulfuric acid; propionic acid / ethyl acetate / -20 °C 1.3: 40 - 45 °C 2.1: 3-Methylpyridine / dichloromethane / 0 °C 3.1: ammonium carbamate / Novozyme 435 / dichloromethane; acetonitrile / 40 °C / Enzymatic reaction 4.1: triethylamine; hydrogen; sulfur trioxide trimethylamine complex / palladium-on-charcoal / isopropyl alcohol; water 5.1: sodium 2-ethylhexanoic acid / ethanol; water View Scheme
Multi-step reaction with 5 steps 1.1: sodium tetrahydroborate; sulfuric acid; propionic acid / ethyl acetate / -20 °C 1.3: 40 - 45 °C 2.1: ammonia / methanol / 20 °C 3.1: N-ethyl-N,N-diisopropylamine; (fluorenylmethoxy)carbonyl chloride / chlorobenzene / 30 °C 4.1: triethylamine; hydrogen; sulfur trioxide trimethylamine complex / palladium-on-charcoal / isopropyl alcohol; water 5.1: sodium 2-ethylhexanoic acid / ethanol; water View Scheme
Multi-step reaction with 6 steps 1.1: sodium tetrahydroborate; sulfuric acid; propionic acid / ethyl acetate / -20 °C 1.3: 40 - 45 °C 2.1: ammonia / methanol / 20 °C 3.1: N-ethyl-N,N-diisopropylamine; (fluorenylmethoxy)carbonyl chloride / chlorobenzene / 30 °C 4.1: hydrogen / 5% Pd-C / dichloromethane; N,N-dimethyl-formamide / 2250.23 Torr 5.1: water 6.1: sodium 2-ethylhexanoic acid / ethanol; water View Scheme

(2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octan-2-carboxylic acid ethyl ester (1416134-63-8) → (2S,5R)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide 7-oxo-6-(sulfoxy)monosodium salt (1192491-61-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: ammonium carbamate / Novozyme 435 / dichloromethane; acetonitrile / 40 °C / Enzymatic reaction 2: triethylamine; hydrogen; sulfur trioxide trimethylamine complex / palladium-on-charcoal / isopropyl alcohol; water 3: sodium 2-ethylhexanoic acid / ethanol; water View Scheme
Multi-step reaction with 4 steps 1.1: ammonium carbamate / Novozyme 435 / dichloromethane; acetonitrile / 40 °C / Enzymatic reaction 2.1: hydrogen / 5% Pd-C / dichloromethane; N,N-dimethyl-formamide 2.2: 20 °C 2.3: pH > 6 3.1: dichloromethane; water 4.1: sodium 2-ethylhexanoic acid / ethanol; water View Scheme
Multi-step reaction with 4 steps 1: ammonium carbamate / Novozyme 435 / dichloromethane; acetonitrile / 40 °C / Enzymatic reaction 2: hydrogen / 5% Pd-C / dichloromethane; N,N-dimethyl-formamide / 2250.23 Torr 3: water 4: sodium 2-ethylhexanoic acid / ethanol; water View Scheme
Multi-step reaction with 4 steps 1.1: lithium hydroxide / 1 h / 10 - 20 °C 2.1: hydrogenchloride / dichloromethane; water 3.1: ammonia; sodium sulfate; triethylamine / -25 - 5 °C 4.1: 10 wt% Pd(OH)2 on carbon; ammonium formate / 5 h / 30 - 40 °C / Inert atmosphere 4.2: 4 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: lithium hydroxide monohydrate; water / tetrahydrofuran / 1 h / -5 - 5 °C 2.1: triethylamine; isobutyl chloroformate; ammonium hydroxide / dichloromethane / 1 h / -10 - 20 °C 3.1: triethylamine; triethylamine sulfur trioxide; palladium 10% on activated carbon; hydrogen / isopropyl alcohol; water / 20 °C / Sealed tube 3.2: 1 h / 20 °C / Sealed tube 4.1: sodium isooctanoate / water; ethanol / 4 h / 35 - 40 °C View Scheme

(2S,5R)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide 7-oxo-6-(sulfoxy)monosodium salt (1192491-61-4) + tetra(n-butyl)ammonium hydroxide (2052-49-5) → ({[(2S,5R)-2-carbamoyl-7-oxo-6-(sulfooxy)-1,6-diazabicyclo[3,2,1]-oct-6-yl]oxy}sulfonyl)tetrabutylammonium salt (1192651-80-1, 1416134-53-6)

Conditions	Yield
In water at 20 - 25℃;	91.1%

(2S,5R)-1,6-diazabicyclo[3.2.1]octane-2-carboxamide 7-oxo-6-(sulfoxy)monosodium salt (1192491-61-4) + tetrabutylammonium acetate (10534-59-5) → ({[(2S,5R)-2-carbamoyl-7-oxo-6-(sulfooxy)-1,6-diazabicyclo[3,2,1]-oct-6-yl]oxy}sulfonyl)tetrabutylammonium salt (1192651-80-1, 1416134-53-6)

Conditions	Yield
In water at 20 - 25℃;	89%

Upstream product

• 1383814-54-7 (2S,5R)-tert-butyl 5-(benzyloxyamino)-1-(2,2,2-trifluoroacetyl)piperidine-2-carboxylate 
• 1383814-55-8 (2S,5R)-tert-butyl 5-(benzyloxyamino)piperidine-2-carboxylate 
• 1383814-56-9 (2S,5R)-tert-butyl 6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylate 
• 1383814-57-0 (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid cyclohexylamine salt 
• 32159-21-0 Cbz-L-pGlu-OH 
• 1174020-25-7 (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid 
• 1383814-59-2 (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octan-2-carboxylic acid allyl ester 
• 1383814-60-5 (2S,5R)-6-benzyloxy-7-oxo-1,6-diazabicyclo[3.2.1]octan-2-carboxylic acid 2,5-dioxopyrrolidin-1-yl ester 
• 81470-51-1 tert-butyl N-benzyloxycarbonyl-L-pyroglutamate 
• 1192651-79-8 avibactam 

Downstream Products

• 1192651-80-1 ({[(2S,5R)-2-carbamoyl-7-oxo-6-(sulfooxy)-1,6-diazabicyclo[3,2,1]-oct-6-yl]oxy}sulfonyl)tetrabutylammonium salt 

Relevant articles and documents

Orally Absorbed Derivatives of the β-Lactamase Inhibitor Avibactam. Design of Novel Prodrugs of Sulfate Containing Drugs

Only one FDA-approved β-lactamase inhibitor has ever been orally available: clavulanic acid, approved in 1984. Avibactam, approved by FDA in 2015, is the first of a new class of BLIs called diazabicyclooctanes, or "DBOs". This class has much broader coverage than clavulanic acid but can only be administered by intravenous injection. Herein, we describe the synthesis and testing of the first approved BLI to be rendered orally bioavailable since clavulanic acid (1984).

RETRACTED ARTICLE: A New Synthetic Route to Avibactam: Lipase Catalytic Resolution and the Simultaneous Debenzylation/Sulfation

An efficient synthesis of avibactam starting from commercially available ethyl-5-hydroxypicolinate was completed in 10 steps and 23.9% overall yield. The synthesis features a novel lipase-catalyzed resolution, in the preparation of (2S,5S)-5-hydroxypiperidine-2-carboxylate acid, which is a valuable precusor of the key intermediate ethyl (2S,5R)-5-((benzyloxy)amino)piperidine-2-carboxylate. An optimized one-pot debenzylation/sulfation reaction, followed by cation exchange, gave the avibactam sodium salt on a 400.0 g scale.

Preparation method of avibactam sodium

The invention discloses a synthesis method of avibactam sodium. (2S,5R)-benzyloxyamino piperidine-2-ethyl formate oxalate (I) is used as an initial raw material; and the method comprises the followingsteps: reacting the raw material with a protecting group, carrying out carbonylation cyclization, carrying out hydrolysis of ester, ammoniating, sulfonating with a sulfur trioxide complex, salifyingwith an ammonium ion source, and salifying with a sodium salt to obtain avibactam sodium, and has the advantages of simple operation, easily controlled conditions, easy industrial production and wideapplication prospect.

Avibactam intermediate compound disulfonic acid gemini quaternary ammonium salt and preparation method thereof

The invention discloses an avibactam intermediate compound, disulfonic acid gemini quaternary ammonium salt, and a preparation method thereof, and relates to medical compounds and organic chemical synthesis, and the preparation method of the avibactam intermediate compound disulfonic acid gemini quaternary ammonium salt comprises the following steps: (1) carrying out hydrogenolysis sulfonation reaction on (2S,5R)-6-hydroxy-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-formamide; (2) after the reaction in the previous step is completed, performing suction filtration, washing filtrate once, and adding gemini quaternary ammonium salt for reaction; and (3) after the reaction in the previous step is completed, carrying out extraction, rotary evaporation and crystallization. Compared with the prior art,the method has the advantages that the operation is simple, the raw materials are easy to obtain, the cost is lower, the dosage of the gemini quaternary ammonium salt is lower, the purity of the obtained disulfonic acid gemini quaternary ammonium salt is higher, and the HPLC relative purity of avibactam sodium generated by sodium salt exchange of the disulfonic acid gemini quaternary ammonium salt is greater than 99.5%, so that the process is suitable for large-scale production.