122547-49-3

Basic information

• Product Name: Faropenem sodium
• Synonyms: (5R,6S,8R,2′R)-2-(2′-tetrahydrofuryl)-6-hydroxyethylpenem-3-carboxylate sodium salt;Faropenem sodium hydrate;sodiuM (5S,6R)-6-((S)-1-hydroxyethyl)-7-oxo-3-((R)-tetrahydrofuran-2-yl)-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate;(5r,6s)-6-(1(r)-hydroxyethyl)-2-(2(r)-tetrahydrofuryl)penem-3-carboxylicacid;6-(1-hydroxyethyl)-7-oxo-3-(tetrahydro-2-furanyl)-,monosodiumsalt,(5r-(3(r*),5-alpha,6-alpha(r*)4-thia-1-azabicyclo(3.2.0)hept-2-ene-2-carboxylicaci;alp201;fropenumsodium;o-3-(tetrahydro-2-furanyl)-,monosodiumsalt,(5r-(3(r*),5-alpha,6-alpha(r*)))
• CAS NO: 122547-49-3
• Molecular Formula: C₁₂H₁₄NO₅S*Na
• Molecular Weight: 307.3
• EINECS: 1592732-453-0
• Product Categories: Pharmaceutical intermediates;chiral;Cnbio;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 122547-49-3.mol
• Article Data: 5

Chemical Properties

• Boiling Point: 570.2 °C at 760 mmHg
• Flash Point: 298.7 °C
• Appearance: white to light brown/
• Vapor Pressure: 2.23E-15mmHg at 25°C
• Storage Temp.: ?20°C
• Solubility: H2O: ≥20mg/mL
• Stability: Hygroscopic
• CAS DataBase Reference: Faropenem sodium(CAS DataBase Reference)
• NIST Chemistry Reference: Faropenem sodium(122547-49-3)
• EPA Substance Registry System: Faropenem sodium(122547-49-3)

Safety Data

• WGK Germany: 3
• Hazardous Substances Data: 122547-49-3(Hazardous Substances Data)

Usage

Description

Faropenem sodium is an orally active beta-lactam antibiotic that belongs to the penem group. It is available in the form of faropenem sodium hydrate and is prescribed for oral usage. Faropenem sodium is effective against Enterobacteriaceae bacterial infections that exhibit cephalosporin resistance. It is particularly useful in treating urinary tract infections caused by extended-spectrum beta-lactamases (ESBL) producing bacteria. Faropenem sodium is characterized by its pale yellow crystalline appearance.

Uses

Used in Pharmaceutical Industry:
Faropenem sodium is used as an antibiotic for the treatment of bacterial infections, particularly those caused by ESBL-producing bacteria. Its effectiveness against cephalosporin-resistant Enterobacteriaceae makes it a valuable addition to the arsenal of antibiotics available for combating resistant infections.
Used in Urology:
Faropenem sodium is used as a therapeutic agent for treating urinary tract infections. Its ability to target ESBL-producing bacteria makes it a preferred choice for addressing infections that are resistant to other commonly prescribed antibiotics.
Used in Research and Development:
Faropenem sodium is utilized in the research and development of new antibiotics and treatment strategies for bacterial infections. Its unique properties and effectiveness against resistant bacteria make it a promising candidate for further study and potential development of new drugs and therapies.

Biochem/physiol Actions

Faropenem sodium is an ultra-broad spectrum, β-lactamase resistant, β-lactam antibiotic active against both Gram-positive and Gram-negative bacteria.

InChI:InChI=1/C12H15NO5S.Na/c1-5(14)7-10(15)13-8(12(16)17)9(19-11(7)13)6-3-2-4-18-6;/h5-7,11,14H,2-4H2,1H3,(H,16,17);/q;+1/p-1/t5-,6-,7+,11-;/m1./s1

Synthetic route

(5R,6S)-6-((R)-1-hydroxyethyl)-2-((R)-tetrahydro-2-furyl)penem-3-carboxylic acid allyl ester (106559-80-2) → Furopenem (122547-49-3)

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; triphenylphosphine; sodium 2-ethylhexanoic acid In water; ethyl acetate at 20℃; for 5h; Inert atmosphere; Large scale reaction;	86.5%
Stage #1: (5R,6S)-6-((R)-1-hydroxyethyl)-2-((R)-tetrahydro-2-furyl)penem-3-carboxylic acid allyl ester With sodium isooctanoate; sodium caprylate; triphenylphosphine In dichloromethane; ethyl acetate at 20℃; Stage #2: With tetrakis(triphenylphosphine) palladium(0) In dichloromethane; ethyl acetate at 25 - 30℃; for 0.666667h; Inert atmosphere;	73.3%
With tetrakis(triphenylphosphine) palladium(0); triphenylphosphine; sodium 2-ethylhexanoic acid In ethyl acetate for 1h; Ambient temperature;

(3R,4R)-3-[(R)-1-(tert-butyldimethylsilyloxy)ethyl]-4-acetoxyazetidin-2-one (76899-07-5, 78963-47-0, 78963-48-1, 78963-60-7, 80951-41-3, 81275-02-7, 85647-75-2, 85954-95-6, 92217-74-8, 104527-11-9, 76855-69-1) → Furopenem (122547-49-3)

Conditions	Yield
Multi-step reaction with 5 steps 1: aq. NaHCO3 / acetone / 4 h / 60 °C 2: Et3N / CH2Cl2 / 0.17 h / -20 °C 3: triethyl phosphite / xylene / 11 h / Heating 4: AcOH, tetra-n-butylammonium fluoride / tetrahydrofuran / 8.5 h / 50 °C 5: Ph3P, tetrakis(triphenylphosphine)palladium, sodium 2-ethylhexanoate / ethyl acetate / 1 h / Ambient temperature View Scheme
Multi-step reaction with 5 steps 1: sodium hydroxide / acetone / 2 h / 0 - 20 °C / pH 8 - 10 2: triethylamine / dichloromethane / 2 h / 0 - 5 °C 3: triethyl phosphite / 5,5-dimethyl-1,3-cyclohexadiene / 5 h / Reflux 4: hydrogenchloride; palladium on activated charcoal; hydrogen / methanol / 16 h / 40 °C / 3040.2 Torr 5: sodium 2-ethylhexanoic acid / tetrahydrofuran; water / 2 h / 20 °C View Scheme

R-(+)-thio tetrahydrofuran-2-carboxylic acid → Furopenem (122547-49-3)

Conditions	Yield
Multi-step reaction with 5 steps 1: aq. NaHCO3 / acetone / 4 h / 60 °C 2: Et3N / CH2Cl2 / 0.17 h / -20 °C 3: triethyl phosphite / xylene / 11 h / Heating 4: AcOH, tetra-n-butylammonium fluoride / tetrahydrofuran / 8.5 h / 50 °C 5: Ph3P, tetrakis(triphenylphosphine)palladium, sodium 2-ethylhexanoate / ethyl acetate / 1 h / Ambient temperature View Scheme
Multi-step reaction with 5 steps 1: sodium hydroxide / acetone / 2 h / 0 - 20 °C / pH 8 - 10 2: triethylamine / dichloromethane / 2 h / 0 - 5 °C 3: triethyl phosphite / 5,5-dimethyl-1,3-cyclohexadiene / 5 h / Reflux 4: hydrogenchloride; palladium on activated charcoal; hydrogen / methanol / 16 h / 40 °C / 3040.2 Torr 5: sodium 2-ethylhexanoic acid / tetrahydrofuran; water / 2 h / 20 °C View Scheme

(R)-Tetrahydro-furan-2-carbothioic acid S-{(2R,3S)-3-[(R)-1-(tert-butyl-dimethyl-silanyloxy)-ethyl]-4-oxo-azetidin-2-yl} ester (106560-32-1) → Furopenem (122547-49-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: Et3N / CH2Cl2 / 0.17 h / -20 °C 2: triethyl phosphite / xylene / 11 h / Heating 3: AcOH, tetra-n-butylammonium fluoride / tetrahydrofuran / 8.5 h / 50 °C 4: Ph3P, tetrakis(triphenylphosphine)palladium, sodium 2-ethylhexanoate / ethyl acetate / 1 h / Ambient temperature View Scheme
Multi-step reaction with 4 steps 1: triethylamine / dichloromethane / 2 h / 0 - 5 °C 2: triethyl phosphite / 5,5-dimethyl-1,3-cyclohexadiene / 5 h / Reflux 3: hydrogenchloride; palladium on activated charcoal; hydrogen / methanol / 16 h / 40 °C / 3040.2 Torr 4: sodium 2-ethylhexanoic acid / tetrahydrofuran; water / 2 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1: triethylamine / dichloromethane / 3 h / -20 - -15 °C 2: triethyl phosphite / 5,5-dimethyl-1,3-cyclohexadiene / 4.5 h / 150 °C 3: acetic acid; tetrabutyl ammonium fluoride / tetrahydrofuran / 4 h / 30 °C 4: palladium 10% on activated carbon; sodium hydrogencarbonate; hydrogen / ethyl acetate; water / 16 h / 25 - 35 °C View Scheme

allyl (5R,6S)-6((R)-1-t-butyldimethylsilyloxyethyl)-7-oxo-3-((R)-2-tetrahydrofuryl)-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (120705-67-1) → Furopenem (122547-49-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: AcOH, tetra-n-butylammonium fluoride / tetrahydrofuran / 8.5 h / 50 °C 2: Ph3P, tetrakis(triphenylphosphine)palladium, sodium 2-ethylhexanoate / ethyl acetate / 1 h / Ambient temperature View Scheme

(3S,4R)-1-(allyloxy)oxoacetyl-3-((R)-1-hydroxyethyl)-4-((R)-2-tetrahydrofuranyl)carbonylthio-azetidin-2-one (429691-43-0) → Furopenem (122547-49-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: triethyl phosphite / xylene / 11 h / Heating 2: AcOH, tetra-n-butylammonium fluoride / tetrahydrofuran / 8.5 h / 50 °C 3: Ph3P, tetrakis(triphenylphosphine)palladium, sodium 2-ethylhexanoate / ethyl acetate / 1 h / Ambient temperature View Scheme

faropenem (106560-14-9) → Furopenem (122547-49-3)

Conditions	Yield
With sodium 2-ethylhexanoic acid In tetrahydrofuran; water at 20℃; for 2h;	125 g

C25H34N2O9SSi → Furopenem (122547-49-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: triethyl phosphite / 5,5-dimethyl-1,3-cyclohexadiene / 5 h / Reflux 2: hydrogenchloride; palladium on activated charcoal; hydrogen / methanol / 16 h / 40 °C / 3040.2 Torr 3: sodium 2-ethylhexanoic acid / tetrahydrofuran; water / 2 h / 20 °C View Scheme

C19H21NO5S → Furopenem (122547-49-3)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen; sodium hydrogencarbonate In water; ethyl acetate at 25 - 35℃; for 16h;

C25H35NO7SSi → Furopenem (122547-49-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: triethyl phosphite / 5,5-dimethyl-1,3-cyclohexadiene / 4.5 h / 150 °C 2: acetic acid; tetrabutyl ammonium fluoride / tetrahydrofuran / 4 h / 30 °C 3: palladium 10% on activated carbon; sodium hydrogencarbonate; hydrogen / ethyl acetate; water / 16 h / 25 - 35 °C View Scheme

Furopenem (122547-49-3) + 4-chloromethyl-5-methyl-1,3-dioxol-2-one (80841-78-7) → faropenem medoxomil

Conditions	Yield
With sodium hydrogencarbonate; potassium iodide; benzyltri(n-butyl)ammonium chloride In tetrahydrofuran at 30 - 55℃; for 5h;	99.11%
With sodium hydrogencarbonate; potassium iodide; tetrabutyl-ammonium chloride In acetone at 50℃; for 4h; Conversion of starting material;	94.2%
With benzyltri(n-butyl)ammonium chloride; sodium hydrogencarbonate; potassium iodide In tetrahydrofuran at 30 - 55℃; for 6h; Product distribution / selectivity;	70%
With sodium hydrogencarbonate; benzyltri(n-butyl)ammonium chloride In tetrahydrofuran at 50℃; for 4h; Conversion of starting material;	36.7%

Furopenem (122547-49-3) → Sodium; (5S,6S)-6-((R)-1-hydroxy-ethyl)-7-oxo-3-(R)-tetrahydro-furan-2-yl-4-thia-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylate (133885-56-0)

Conditions	Yield
In water Irradiation;

chlorosulfuric acid chloromethyl ester (49715-04-0) + Furopenem (122547-49-3) + tetrabutylammonium sulfate (2472-88-0) → chloromethyl (5R,6S)-6-[(R)-1-hydroxyethyl]-2-[(R)-2-tetrahydrofuryl]penem-3-carboxylate (141706-77-6)

Conditions	Yield
With potassium hydrogencarbonate In dichloromethane; water

Furopenem (122547-49-3) + (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl iodide (80841-79-8) → (5-Methyl-2-oxo-1,3-dioxolen-4-yl)methyl (5R,6S)-6-[(R)-1-hydroxyethyl]-2-[(R)-2-tetrahydrofuryl]penem-3-carboxylate

Conditions	Yield
In water; N,N-dimethyl-formamide

Upstream product

• 106560-14-9 faropenem 
• 429691-43-0 (3S,4R)-1-(allyloxy)oxoacetyl-3-((R)-1-hydroxyethyl)-4-((R)-2-tetrahydrofuranyl)carbonylthio-azetidin-2-one 
• 120705-67-1 allyl (5R,6S)-6((R)-1-t-butyldimethylsilyloxyethyl)-7-oxo-3-((R)-2-tetrahydrofuryl)-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate 
• 106560-32-1 (R)-Tetrahydro-furan-2-carbothioic acid S-{(2R,3S)-3-[(R)-1-(tert-butyl-dimethyl-silanyloxy)-ethyl]-4-oxo-azetidin-2-yl} ester 
• 153165-72-1 R-(+)-thio tetrahydrofuran-2-carboxylic acid 
• 76899-07-5 (3R,4R)-3-[(R)-1-(tert-butyldimethylsilyloxy)ethyl]-4-acetoxyazetidin-2-one 
• 106559-80-2 (5R,6S)-6-((R)-1-hydroxyethyl)-2-((R)-tetrahydro-2-furyl)penem-3-carboxylic acid allyl ester 

Downstream Products

• 133885-56-0 Sodium; (5S,6S)-6-((R)-1-hydroxy-ethyl)-7-oxo-3-(R)-tetrahydro-furan-2-yl-4-thia-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylate 

Relevant articles and documents

An efficient method for removal of residual palladium from organic solution of faropenem sodium in the Pd(II)-catalyzed cleavage of allyl faropenem

An improved palladium(II)-catalyzed cleavage of the allyl group in allyl faropenem 2 into faropenem sodium 1 is described. The development of an efficient method for the removal of palladium impurities from the crude product 1 upon treatment with polystyrene-bound 2,4,6-trimercapto-s-triazine (polystyrene-bound TMT) led to a drastic decrease of residual palladium level from 1500-1600 ppm to less than 10 ppm in the final isolated product. The palladium(II)-catalyzed cleavage and palladium removal process demonstrated on 10 kg scale are highly convenient and efficient.

A synthesis method of faropenem sodium

The invention provides a method for synthesizing faropenem sodium. According to the method, oxalic acid chloride p-nitrobenzyl ester is used for replacing allyloxy oxalyl chloride in a conventional process, and thus the generation of polymer impurities is effectively prevented, and the raw material conversion rate and the product yield are increased; by adopting a method of catalytic hydrogenation under an acidic condition, silylation protection groups and p-nitrobenzyl ester protection groups are removed, organophosphorus impurities which are difficult to treat are effectively prevented, the separation and purification of products are facilitated, the maneuverability is improved, and the industrialized production is facilitated.

Structure-activity relationships of penem antibiotics: crystallographic structures and implications for their antimicrobial activities

Twelve closely related crystal structures of the penem derivatives revealed a characteristic short contact of the oxygen atom in the C2 side-chains with the S1 atom. The side-chain conformations of the crystal structures showed a good correlation with the antimicrobial activity. In particular, the penems which show high antimicrobial activity have similar torsion angles for S1-C2-C1'-C2', suggesting that the disposition of the C2' atom would be important for binding to penicillin-interacting enzymes. Two conformations of the C6 hydroxyethyl group were observed in the crystal structures. Of those two, the conformation with a larger torsion angle (δ = 179.2°) is deduced to be the enzyme-bound conformation in the Michaelis complex.