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ChemSpider 2D Image | Cefadroxil | C16H17N3O5S



  • Molecular FormulaC16H17N3O5S
  • Average mass363.388 Da
(6R,7R)-7-{[(2R)-2-Amino-2-(4-hydroxyphenyl)acetyl]amino}-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
256-555-6 [EINECS]
50370-12-2 [RN]
5-Thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid, 7-(((2R)-amino(4-hydroxyphenyl)acetyl)amino)-3-methyl-8-oxo-, (6R,7R)-
5-Thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, 7-[[(2R)-2-amino-2-(4-hydroxyphenyl)acetyl]amino]-3-methyl-8-oxo-, (6R,7R)-
цефадроксил [Russian] [INN]
سيفادروكسيل [Arabic] [INN]
头孢羟氨苄 [Chinese] [INN]

ChemSpider 2D Image | Cephos | C16H19N3O6S


  • Molecular FormulaC16H19N3O6S
  • Average mass381.404 Da
5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, 7-[[(2R)-2-amino-2-(4-hydroxyphenyl)acetyl]amino]-3-methyl-8-oxo-, (6R,7R)-, monohydrate
66592-87-8 [RN]
(6R,7R)-7-{[(2R)-2-amino-2-(4-hydroxyphenyl)acetyl]amino}-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid hydrate
(6R,7R)-7-{[(2R)-2-Amino-2-(4-hydroxyphenyl)acetyl]amino}-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid hydrate (1:1)

Product Ingredients

Cefadroxil hemihydrate J9CMF6461M 119922-85-9 AJAMDISMDZXITN-QXBGZBSVSA-N
Cefadroxil monohydrate 280111G160 66592-87-8 NBFNMSULHIODTC-CYJZLJNKSA-N
Cefadroxil sodium SSZ6380I0I 42284-83-3 GQOVFIUWRATNJC-CYJZLJNKSA-M
CAS Registry Number: 66592-87-8
CAS Name: (6R,7R)-7-[[(2R)-Amino-(4-hydroxyphenyl)acetyl]amino]-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid monohydrate
Additional Names: 7-[D-(-)-a-amino-a-(4-hydroxyphenyl)acetamido]-3-methyl-3-cephem-4-carboxylic acid monohydrate; p-hydroxycephalexine monohydrate
Manufacturers’ Codes: BL-S578; MJF-11567-3
Trademarks: Baxan (BMS); Bidocef (BMS); Cefa-Drops (Fort Dodge); Cefamox (BMS); Ceforal (Farmoffer); Cephos (CT); Duracef (BMS); Duricef (BMS); Kefroxil (Torre); Oracéfal (BMS); Sedral (BMS); Ultracef (BMS)
Molecular Formula: C16H17N3O5S.H2O
Molecular Weight: 381.40
Percent Composition: C 50.39%, H 5.02%, N 11.02%, O 25.17%, S 8.41%
Literature References: Semi-synthetic cephalosporin antibiotic. Prepn: NL 6812382; L. B. Crast, Jr., US 3489752 (1969, 1970 both to Bristol-Myers); T. Takahashi et al., DE 2216113eidem, US 3816253 (1972, 1974, both to Takeda). Prepn of crystalline monohydrate: D. Bouzard et al., US 4504657 (1985 to Bristol-Myers). Antimicrobial activity: R. E. Buck, K. E. Price, Antimicrob. Agents Chemother. 11, 324 (1977). Pharmacology: M. Pfeffer et al., ibid. 331; A. I. Hartstein et al., ibid. 12, 93 (1977). Review: J. Antimicrob. Chemother. 10, Suppl. B, 1-162 (1982). Series of articles on clinical trials in respiratory tract infections: Drugs 32, Suppl. 3, 1-56 (1986).
Properties: White crystals, mp 197° (dec).
Melting point: mp 197° (dec)
Therap-Cat: Antibacterial.
Therap-Cat-Vet: Antibacterial.
Keywords: Antibacterial (Antibiotics); ?Lactams; Cephalosporins.


Cefadroxil is a cephalosporin antibiotic used in the treatment of various bacterial infections, such as urinary tract infections, skin and skin structure infections, and tonsillitis.

Cefadroxil (formerly trademarked as Duricef) is a broad-spectrum antibiotic of the cephalosporin type, effective in Gram-positive and Gram-negative bacterial infections. It is a bactericidal antibiotic.

It was patented in 1967 and approved for medical use in 1978.[1]

DURICEF (cefadroxil) is a semisynthetic cephalosporin antibiotic intended for oral administration. It is a white to yellowish-white crystalline powder. It is soluble in water and it is acid- stable. It is chemically designated as 5-Thia-l-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, 7-[[amino(4-hydroxyphenyl)acetyl]amino]-3-methyl-8-oxo-, monohydrate[6R- [6α,7β(R*)]]-. It has the formula C16H17N3O5S•H20 and the molecular weight of 381.40. It has the following structural formula:


DURICEF (cefadroxil monohydrate) structural formula illustration

DURICEF (cefadroxil) film-coated tablets, 1 g, contain the following inactive ingredients: microcrystalline cellulose, hydroxypropyl methylcellulose, magnesium stearate, polyethylene glycol, polysorbate 80, simethicone emulsion, and titanium dioxide.

DURICEF (cefadroxil) for Oral Suspension contains the following inactive ingredients: FD&C Yellow No. 6, flavors (natural and artificial), polysorbate 80, sodium benzoate, sucrose, and xanthan gum.

DURICEF (cefadroxil) capsules contain the following inactive ingredients: D&C Red No. 28, FD&C Blue No. 1, FD&C Red No. 40, gelatin, magnesium stearate, and titanium dioxide.


a) : IR spectrum of pure cefadroxil drug. 

IR spectrum of pure cefadroxil drug.

Synthesis Reference

Leonardo Marsili, “Substantially anhydrous crystalline cefadroxil and method for producing it.” U.S. Patent US5329001, issued April, 1978.





R.S. Vardanyan, V.J. Hruby, in Synthesis of Essential Drugs, 2006


Cefadroxil, [6R-[6α,7β(R)]]-3-methyl-8-oxo-7-[[amino(4-hydroxyphenyl) acetyl]amino]-5-thia-1-azabicyclo[4.2.0]oct-2-en-2-carboxylic acid (, is an analog of cephalexin and differs only in the presence of a hydroxyl group in the fourth position of the phenyl ring of phenylglycine, and is synthesized by a scheme analogous to the scheme of cephradin synthesis [90–96].

Cefadroxil has a broad spectrum of antimicrobial action; it is active with respect to Gram-positive and Gram-negative microorganisms. Like all of the other drugs described above, it acts as a bactericide by disrupting the process of restoring the membranes of bacteria. Synonyms of this drug are bidocef, cefadril, duracef, ultracef, and others.



    • ATC:J01DA09
  • MW:363.39 g/mol
  • CAS-RN:50370-12-2
  • InChI:InChI=1S/C16H17N3O5S/c1-7-6-25-15-11(14(22)19(15)12(7)16(23)24)18-13(21)10(17)8-2-4-9(20)5-3-8/h2-5,10-11,15,20H,6,17H2,1H3,(H,18,21)(H,23,24)/t10-,11-,15-/m1/s1
  • EINECS:256-555-6
  • LD50:>1.5 g/kg (M, i.v.); >10 g/kg (M, p.o.);
    >1 g/kg (R, i.v.); >10 g/kg (R, p.o.);
    >2 g/kg (dog, p.o.)



CAS-RN Formula Chemical Name CAS Index Name
22252-43-3 C8H10N2O3S 7-amino-3-deacetoxycephalosporanic acid 5-Thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, 7-amino-3-methyl-8-oxo-, (6R-trans)-
53487-89-1 C13H15NO5 d(–)-4-hydroxy-N-(2-methoxycarbonyl-1-methylethenyl)phenylglycine Benzeneacetic acid, 4-hydroxy-α-[(3-methoxy-1-methyl-3-oxo-1-propenyl)amino]-, (R)-


 Seo, Dae-Won; WO 2005042543


Oral cephalosporin antibiotics, including cefprozil, cefatrizine, and cefadroxii, commonly have a 4-hydroxyphenylglycine group, as represented by the following formula:
Figure imgf000002_0001

The compound of the above formula is cefprozil when A is -C=CH-CH3, cefatrizine when A is 1 H-1 ,2,3-triazole-4-yl-thiomethyl, and cefadroxii when A is -CH3. Conventionally, there have been known various processes for preparing oral cephalosporin antibiotics, such as cefprozil, cefatrizine, and cefadroxii, by reacting reactive derivatives of 4-hydroxyphenylglycine with 3-cephem compounds. For example, U.S. Patent No. 3,985,741 discloses a process for preparing a cefadroxii, which includes reacting 4-hydroxyphenylglycine and ethylchloroformate in

N-methylmorpholine to obtain an anhydride, followed by reaction with
7-amino-deacetoxy-cephalosporanic acid (7-ADCA). However, the yield and quality of the product are poor. U.S. Patent Nos. 4,520,022, 4,591 ,641 , and 4,661 ,590 disclose a condensation reaction between 4-hydroxyphenylglycine with a protected amino group and a cephem compound in the presence of Λ/.Λ/’-dicyclohexylcarbodimide. However,
Λ/,Λ/’-dicyclohexylurea produced after the condensation reaction is not easily removed, which restricts industrial applications. U.S. Patent No. 4,336,376 discloses a process for preparing a cefadroxii, which includes reacting a 4-hydroxyphenylglycine salt having a protected amino group with trimethylsilyl-2-oxazolidinone to protect a 4-hydroxyl group followed by reaction with acylchloride to obtain a 4-hydroxyphenylglycine anhydride and then reaction with 7-ADCA. However, silylation is prerequisite and these reactions are annoying, and thus, this process is not suitable for industrial application. U.S. Patent No. 4,708,825 discloses a technique of reacting
4-hydroxyphenylglycine having a substituted amino group with thionyl chloride using a gaseous hydrogen chloride to obtain a 4-hydroxyphenylglycyl chloride hydrochloride followed by reaction with a cephem compound. However, handling property of the thionyl chloride and the gaseous hydrogen chloride is poor, and thus, this technique is not suitable for industrial application. U.S. Patent Nos. 3,925,418, 4,243,819, and 4,464,307 disclose a process for producing 4-hydroxyphenylglycine using excess phosgene. However, difficulty in handling of highly toxic phosgene, removal of excess residual phosgene, and control of reaction conditions renders mass production difficult. As a process for preparing a reactive anhydride of 4-hydroxyphenylglycine, there are reported a method for the preparation of acid chloride using phosphorus pentachloride, phosphorus oxychloride, or thionyl chloride, and a method for the preparation of active ester using imidazole, mercaptobenzothiazole, or hydroxybenzotriazole. However, an acid chloride of 4-hydroxyphenylglycine has poor reactivity due to a hydroxyl group and an active ester of 4-hydroxyphenylglycine has poor reactivity and involves a side reaction. In addition, Korean Patent Laid-Open Publication Nos. 2002-69431 , 2002-69432, 2002-69437, and 2002-69440 disclose a process for preparing a pivaloyl or succinimide derivative of 4-hydroxyphenylglycine and a process for preparing a cephem compound such as cefprozil using the pivaloyl or succinimide derivative of 4-hydroxyphenylglycine. Meanwhile, there have been known various preparation processes for 3-(Z)-propenyl cephem derivative which is a compound useful as an intermediate for preparation of cefprozil which is an oral cephalosporin antibiotic. WO93/16084 discloses a process of selectively separating a 3-(Z)-propenyl cephem compound by means of a hydrochloride, metal, or tertiary amine salt of
7-amino-3-(1-propen-1-yl)-3-cephem-carboxylic acid or by adsorption chromatography. However, there is a disadvantage in that separation and purification are cost-ineffective. U.K. Patent No. 2,135,305 discloses a process for preparing cefprozil from a
4-hydroxyphenylglycine compound with a t-butoxycarbonyl-protected amino group and a cephem compound with a benzhydryl-protected carboxyl group. However, incorporation of a 3-propenyl group after acylation lowers reaction efficiency and high-performance liquid chromatography is required for isomer separation, which render industrial application difficult. U.S. Patent No. 4,727,070 discloses a technique of removing an E-isomer cefprozil from a mixture of 27E cefprozil, which includes incorporating an active group such as sodium imidazolidinone into the mixture of 2VE cefprozil by reaction of the mixture of 27E cefprozil with acetone followed by deprotection. However, purification by chromatography incurs enormous costs. In view of the above problems, Korean Patent Laid-Open Publication No.
2002-80838 discloses a process for preparing a 3-(Z)-propenyl cephem compound by reacting a phosphoranylidene cephem compound with acetaldehyde in a mixed solvent essentially consisting of ether in the presence of a base. According to a disclosure in this patent document, ether is essentially used. In this respect, in the case of using methylenechloride or tetrahydrofuran, even when other reaction conditions, for example, reaction temperature, reaction duration, base, catalyst, and the like are adjusted, it is very difficult to adjust the content of the Z-isomer to more than 83%.
DETAILED DESCRIPTION OF THE INVENTION Technical Goal of the Invention The present invention provides a process for simply preparing a cephalosporin antibiotic in high yield and purity using a novel reactive intermediate, i.e., a 4-hydroxyphenylglycine derivative. The present invention also provides a novel reactive intermediate, i.e., a 4-hydroxyphenylglycine derivative which is used in simply preparing a cephalosphorin antibiotic in high yield and purity, and a preparation process thereof. While searching for a process for stereospecifically preparing a novel
3-(Z)-propenyl cephem derivative, the present inventors found that use of a mixed solvent including methylenechloride, isopropylalcohol, and water in a predetermined ratio can stereospecifically and efficiently produce the 3-(Z)-propenyl cephem derivative, which is in contrary to the disclosure in Korean Patent Laid-Open Publication No. 2002-80838. Therefore, the present invention also provides a process for stereospecifically preparing a 3-(Z)-propenyl cephem derivative using a mixed solvent including methylenechloride, isopropylalcohol, and water in a predetermined ratio.
Figure imgf000007_0002
Figure imgf000009_0003Figure imgf000012_0002
 Example 9 Preparation of
7-r2-amino-2-(4-hvdroxyphenyl)acetamido1-3-methyl-3-cephem-4-carboxylic acid
(cefadroxii) The reaction solution obtained in step A of Example 1 was cooled to -40 °C and a solution obtained by dissolving 6.21 g (0.029mol) of 7-amino-3-methyl-3-cephem-4-carboxylic acid in 40 ml of methylenechloride, 10 ml of water, and 6.5 g of triethylamine was gradually dropwise added thereto for 1 hour. Then, the reaction mixture was incubated at the same temperature for 2 hours and cooled to 0°C to obtain an insoluble solid. The insoluble solid was filtered. A filtrate was sent to a reactor and then stirred for 1 hour after addition of 20 ml of 6N HCI. The reaction solution was adjusted to pH of 3.2 by addition of 10% NaOH, stirred at
0°C for 2 hours, and filtered to give 9.1g (83%) of the titled compound as a white solid. H-NMR( δ , D20-d2) : 1.79(3H, d, 8.6Hz, -CH3), 3.22(1 H, d, 18Hz, 2-H),
3.55(1 H. d. 18Hz, 2-H), 5.15(1 H, d, 4.6Hz, 6-H), 5.66(1 H, d, 4.6Hz, 7-H), 6.91 (2H, d,
8.0Hz, phenyl-H), 7.38(2H, d, 8.0Hz, phenyl-H)


Deshmukh, J. H.; Asian Journal of Chemistry 2010, V22(3), P1760-1768 

Journal of the Chinese Chemical Society (Weinheim, Germany), 66(12), 1649-1657; 2019

Journal of the Indian Chemical Society, 93(6), 593-598; 2016

 Biotechnology Letters, 34(9), 1719-1724; 2012


WO 2011113486

By Gupta, Niranjan Lal et alFrom Indian, 184842, 30 Sep 2000


European Journal of Organic Chemistry, (10), 1817-1820; 2001


 Organic Letters, 2(18), 2829-2831; 2000

The cephalosporin antibiotic Cefadroxil can be epimerized at the α-carbon of its amino acid side chain using pyridoxal as the mediator. By clathration with 2,7-dihydroxynaphthalene, the desired diastereomer can be selectively withdrawn from the equilibrating mixture of epimers. In this way, an asymmetric transformation of Cefadroxil can be accomplished. This opens the possibility of the production of Cefadroxil starting from racemic p-hydroxyphenylglycine, in contrast to the current industrial synthesis that employs the d-amino acid in enantiopure form.

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Medical use

Cefadroxil is a first-generation cephalosporin antibacterial drug that is the para-hydroxy derivative of cephalexin, and is used similarly in the treatment of mild to moderate susceptible infections such as the bacterium Streptococcus pyogenes, causing the disease popularly called strep throat or streptococcal tonsillitisurinary tract infectionreproductive tract infection, and skin infections.

Cefadroxil is used as an antibiotic prophylaxis before dental procedures, for patients allergic to penicillins.

Spectrum of bacterial resistance and susceptibility

Cefadroxil has a broad spectrum of activity and has been effective in treating bacteria responsible for causing tonsillitis, and infections of the skin and urinary tract. The following represents MIC susceptibility data for a few medically significant microorganisms.[2]

  • Escherichia coli: 8 μg/ml
  • Staphylococcus aureus: 1 – 2 μg/ml
  • Streptococcus pneumoniae: ≤1 – >16 μg/ml

Side effects

The most common side effects of cefadroxil are diarrhea (which, less commonly, may be bloody), nauseaupset stomach, and vomiting. Other side effects include[3] rasheshives, and itching.


Cefadroxil is almost completely absorbed from the gastrointestinal tract. After doses of 500 mg and 1 g by mouth, peak plasma concentrations of about 16 and 30 micrograms/ml, respectively, are obtained after 1.5 to 2.0 hours. Although peak concentrations are similar to those of cefalexin, plasma concentrations are more sustained. Dosage with food does not appear to affect the absorption of cefadroxil. About 20% of cefadroxil is reported to be bound to plasma proteins. Its plasma half-life is about 1.5 hours and is prolonged in patients with renal impairment.

Cefadroxil is widely distributed to body tissues and fluids. It crosses the placenta and appears in breast milk. More than 90% of a dose of cefadroxil may be excreted unchanged in the urine within 24 hours by glomerular filtration and tubular secretion; peak urinary concentrations of 1.8 mg/ml have been reported after a dose of 500 mg. Cefadroxil is removed by haemodialysis.


Cefadroxil is given by mouth, and doses are expressed in terms of the anhydrous substance; 1.04 g of cefadroxil monohydrate is equivalent to about 1 g of anhydrous cefadroxil.

Veterinary use

It can be used for treating infected wounds on animals. Usually in powder form mixed with water, it has a color and smell similar to Tang. Given orally to animals, the amount is dependent on their weight and severity of infection.


Clinical data
Trade names Duricef
AHFS/Drugs.com Monograph
MedlinePlus a682730
Routes of
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Protein binding plasma protein
Metabolism unknown
Elimination half-life 1.5 hours
CAS Number
PubChem CID
CompTox Dashboard (EPA)
ECHA InfoCard 100.051.397 Edit this at Wikidata
Chemical and physical data
Formula C16H17N3O5S
Molar mass 363.39 g·mol−1
3D model (JSmol)
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////////////CEFADROXIL, цефадроксил سيفادروكسيل 头孢羟氨苄 , BL-S578; MJF-11567-3, BL S578, MJF 11567-3


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