120709-09-3

Basic information

• Product Name: (6R,7R)-7-Amino-8-oxo-3-(1-propenyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
• Synonyms: 7-apra;5-THIA-1-AZABICYCLO[4.2.0]OCT-2-ENE-2-CARBOXYLIC ACID, 7-AMINO-8-OXO-3-(1-PROPENYL)-, (6R,7R)-;(6R,7R)-7-AMINO-8-OXO-3-(1-PROPENYL)-5-THIA-1-AZABICYCLO[4.2.0]OCT-2-ENE-2-CARBOXYLIC ACID;(6 R,7 R)-7-AMIMO-8-OXO-3-(1-PROPENYL)-5-THIA-1-AZABICYCLO[4.2.0]OCT-2-ENE-2-CARBOXYLIC ACID;Cefprozil intermediate;(6R,7R)-7-amino-8-oxo-3-(1-propenyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carbo;IntermediateoftheCefprozil;(6R,7R)-7-AMINO-8-OXO-3-(1-PROPENYL)-5-THIA-1-AZABICYLO[4.2.0]OCT-2-ENE-2-CARBOXYLIC ACID
• CAS NO: 120709-09-3
• Molecular Formula: C₁₀H₁₂N₂O₃S
• Molecular Weight: 240.28
• EINECS: 1312995-182-4
• Mol File: 120709-09-3.mol
• Article Data: 1

Chemical Properties

• Boiling Point: 539.275 °C at 760 mmHg
• Flash Point: 279.944 °C
• Appearance: /
• Density: 1.5 g/cm³
• Refractive Index: 1.685
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• Solubility: Aqueous Base (Slightly), DMSO (Slightly, Heated, Sonicated)
• PKA: 2.84±0.50(Predicted)
• CAS DataBase Reference: (6R,7R)-7-Amino-8-oxo-3-(1-propenyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid(CAS DataBase Reference)
• NIST Chemistry Reference: (6R,7R)-7-Amino-8-oxo-3-(1-propenyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid(120709-09-3)
• EPA Substance Registry System: (6R,7R)-7-Amino-8-oxo-3-(1-propenyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid(120709-09-3)

Safety Data

• Hazardous Substances Data: 120709-09-3(Hazardous Substances Data)

Usage

Uses

7 APCA is a β-lactam compound, which are synthetic intermediates of therapeutically useful β-lactam antibiotics.

InChI:InChI=1/C10H12N2O3S/c1-2-3-5-4-16-9-6(11)8(13)12(9)7(5)10(14)15/h2-3,6,9H,4,11H2,1H3,(H,14,15)/t6-,9-/m1/s1

Synthetic route

acetaldehyde (75-07-0) + 7-Aminocephalosporanic acid (957-68-6) → (6R,7R)-7-amino-3-(propen-1-yl)-3-cephem-4-carboxylic acid (120709-09-3)

Conditions	Yield
Stage #1: 7-Aminocephalosporanic acid With pyridine; 1,1,1,3,3,3-hexamethyl-disilazane In benzene for 2h; Inert atmosphere; Reflux; Stage #2: With trimethylsilyl iodide In benzene at 0℃; for 1h; Stage #3: acetaldehyde Reagent/catalyst; Further stages;	84.24%

(6R,7R)-7-amino-3-(propen-1-yl)-3-cephem-4-carboxylic acid (120709-09-3) + D-2-p-hydroxyphenylglycine methyl ester (37763-23-8) → 7-[2-amino-2-(4-hydroxyphenyl)acetamido]-3-(propen-1-yl)-3-cephem-4-carboxylic acid (92665-29-7)

Conditions	Yield
Stage #1: (7R,8R)-7-amino-3-[propen-1-yl]-3-cephem-4-carboxylic acid With penicillin acylase at 30 - 35℃; for 0.5h; pH=7; Enzymatic reaction; Stage #2: D-2-p-hydroxyphenylglycine methyl ester With sodium lauryl sulfate In 1,4-dioxane at 30 - 35℃; for 2h; Reagent/catalyst;	97.74%

(6R,7R)-7-amino-3-(propen-1-yl)-3-cephem-4-carboxylic acid (120709-09-3) + ((R)-(2-ethoxycarbonyl-1-methyl-vinylamino)-(4-hydroxyphenyl)-acetyloxy)-(triphenyl)phosphonium chloride → cefprozil (121412-77-9) + E-cefprozil (92676-86-3)

Conditions	Yield
Stage #1: (7R,8R)-7-amino-3-[propen-1-yl]-3-cephem-4-carboxylic acid; ((R)-(2-ethoxycarbonyl-1-methyl-vinylamino)-(4-hydroxyphenyl)-acetyloxy)-(triphenyl)phosphonium chloride With triethylamine In dichloromethane; water at -40 - 0℃; for 3h; Stage #2: With hydrogenchloride In dichloromethane; water for 1h; Stage #3: With sodium hydroxide In dichloromethane; water at 0℃; for 2h; pH=3.2;
Stage #1: (7R,8R)-7-amino-3-[propen-1-yl]-3-cephem-4-carboxylic acid; ((R)-(2-ethoxycarbonyl-1-methyl-vinylamino)-(4-hydroxyphenyl)-acetyloxy)-(triphenyl)phosphonium chloride With triethylamine In ISOPROPYLAMIDE; water at -40 - 0℃; for 3h; Stage #2: With hydrogenchloride In ISOPROPYLAMIDE; water for 1h; Stage #3: With sodium hydroxide In ISOPROPYLAMIDE; water at 0℃; for 2h; pH=3.2;

(6R,7R)-7-amino-3-(propen-1-yl)-3-cephem-4-carboxylic acid (120709-09-3) → cefprozil (121412-77-9) + E-cefprozil (92676-86-3)

Conditions	Yield
Stage #1: potassium (R)-(2-ethoxycarbonyl-1-methyl-vinylamino)-(4-hydroxyphenyl)-acetate With pyridine; pivaloyl chloride In DMF (N,N-dimethyl-formamide); dichloromethane at -30℃; for 2h; Stage #2: (7R,8R)-7-amino-3-[propen-1-yl]-3-cephem-4-carboxylic acid With triethylamine In DMF (N,N-dimethyl-formamide); dichloromethane; water at -40 - 0℃; for 3h;

(6R,7R)-7-amino-3-(propen-1-yl)-3-cephem-4-carboxylic acid (120709-09-3) + C12H17NO5 → C22H27N3O7S

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃; for 3h;

Upstream product

• 75-07-0 acetaldehyde 
• 957-68-6 7-Aminocephalosporanic acid 

Downstream Products

• 92665-29-7 7-[2-amino-2-(4-hydroxyphenyl)acetamido]-3-(propen-1-yl)-3-cephem-4-carboxylic acid 
• 121412-77-9 cefprozil 
• 92676-86-3 E-cefprozil 

Relevant articles and documents

Preparation method of cefprozil

The invention relates to a preparation method of cefprozil. A synthesis method comprises the following steps: taking 7-ACA (7-aminocephalosporanic acid) as a starting raw material; after carrying outsilylation protection, carrying out a series of reactions including iodination and the like to generate a compound 2; taking the compound 2 to react with methyl D-(-)-4-hydroxy-phenylglycinate under the catalysis of immobilized penicillin acylase to generate a compound 1, so as to obtain a target product cefprozil. The preparation method provided by the invention has the advantages of moderate reaction conditions, environmental friendliness, high conversion ratio, simple technology and high cis-isomer content.