161715-20-4

Basic information

• Product Name: 4-Nitrobenzyl(1R,5S,6S)-6-[(R)-1-hydroxyethyl]-1-Methyl-2-[1-(1,3-thiazolin-2-yl)azetidin -3-yl]thio-1-carbapen-2-eM-3-carboxylate
• Synonyms: 4-Nitrobenzyl(1R,5S,6S)-6-[(R)-1-hydroxyethyl]-1-Methyl-2-[1-(1,3-thiazolin-2-yl)azetidin -3-yl]thio-1-carbapen-2-eM-3-carboxylate;(4R,5S,6S)-3-[[1-(4,5-Dihydro-2-thiazolyl)-3-azetidinyl]thio]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid (4-nitrophenyl)methyl ester;TebipeneM Condensation CoMpound;Tebipenem Impurity 4;(4R,5S,6S)-4-nitrobenzyl 3-((1-(4,5-dihydrothiazol-2-yl)azetidin-3-yl)thio)-6-((R)-1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate;(1R,5S,6S)-2-((1-(4,5-Dihydrothiazol-2-yl)azetidin-3-yl)thio)-6-((R)-1-hydroxyethyl)-1-methyl-
• CAS NO: 161715-20-4
• Molecular Formula: C₂₃H₂₆N₄O₆S₂
• Molecular Weight: 516.60974
• EINECS: -0
• Mol File: 161715-20-4.mol

Chemical Properties

• Boiling Point: 741.4±70.0 °C(Predicted)
• Appearance: /
• Density: 1.63±0.1 g/cm3 (20 ºC 760 Torr)
• PKA: 14.36±0.20(Predicted)
• CAS DataBase Reference: 4-Nitrobenzyl(1R,5S,6S)-6-[(R)-1-hydroxyethyl]-1-Methyl-2-[1-(1,3-thiazolin-2-yl)azetidin -3-yl]thio-1-carbapen-2-eM-3-carboxylate(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Nitrobenzyl(1R,5S,6S)-6-[(R)-1-hydroxyethyl]-1-Methyl-2-[1-(1,3-thiazolin-2-yl)azetidin -3-yl]thio-1-carbapen-2-eM-3-carboxylate(161715-20-4)
• EPA Substance Registry System: 4-Nitrobenzyl(1R,5S,6S)-6-[(R)-1-hydroxyethyl]-1-Methyl-2-[1-(1,3-thiazolin-2-yl)azetidin -3-yl]thio-1-carbapen-2-eM-3-carboxylate(161715-20-4)

Safety Data

• Hazardous Substances Data: 161715-20-4(Hazardous Substances Data)

Usage

Uses

1. Used in Pharmaceutical Synthesis:
4-Nitrobenzyl(1R,5S,6S)-6-[(R)-1-hydroxyethyl]-1-Methyl-2-[1-(1,3-thiazolin-2-yl)azetidin-3-yl]thio-1-carbapen-2-eM-3-carboxylate is used as an intermediate in the synthesis of Tebipenem Tetrahydrate (T012840), the active metabolite of Tebipenem Pivoxil (T012900). It plays a crucial role in the development of this antibiotic, which is effective against various bacterial infections.
2. Used in Antimicrobial Applications:
In the pharmaceutical industry, 4-Nitrobenzyl(1R,5S,6S)-6-[(R)-1-hydroxyethyl]-1-Methyl-2-[1-(1,3-thiazolin-2-yl)azetidin-3-yl]thio-1-carbapen-2-eM-3-carboxylate contributes to the development of Tebipenem Tetrahydrate, which demonstrates excellent bactericidal activity against β-lactamase-nonproducing, ampicillin-resistant isolates. This makes it a valuable compound in the fight against antibiotic-resistant bacteria.
3. Used in Research and Development:
4-Nitrobenzyl(1R,5S,6S)-6-[(R)-1-hydroxyethyl]-1-Methyl-2-[1-(1,3-thiazolin-2-yl)azetidin -3-yl]thio-1-carbapen-2-eM-3-carboxylate may also be utilized in research and development settings to study its properties, potential applications, and interactions with other molecules. Understanding its characteristics can lead to the discovery of new pharmaceutical compounds and治疗方法 (treatment methods) for various diseases and conditions.

Synthetic route

(4-nitrophenyl)methyl (4R,5R,6S)-3-[(diphenoxyphosphinyl)oxy]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (93711-81-0, 90776-59-3) + 1-(4,5-dihydro-1,3-thiazol-2-yl)-3-mercaptoazetidine hydrochloride → (+)-(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-{[1-(2-thiazolin-2-yl)-3-azetidinyl]mercapto}-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid p-nitrobenzyl ester (161715-20-4)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; acetonitrile at -20℃; for 2h;	94%
With N-ethyl-N,N-diisopropylamine at -20℃; for 3.5h; Temperature;	88.5%
With N-ethyl-N,N-diisopropylamine In acetonitrile

3-methanesulfonyloxy-1-(1,3-thiazolin-2-yl)azetidine (179337-62-3) → (+)-(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-{[1-(2-thiazolin-2-yl)-3-azetidinyl]mercapto}-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid p-nitrobenzyl ester (161715-20-4)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: 88 percent / potassium thioacetate / dimethylformamide / 5.5 h / 100 °C 2.1: KOH / propan-2-ol; methanol / 0.17 h / 5 °C 2.2: 87 percent / HCl / propan-2-ol; methanol / 15 h / 5 °C 3.1: 94 percent / diisopropyl ethylamine; MeCN / 2 h / -20 °C View Scheme

1-(1,3-thiazolin-2-yl-)azetidin-3-ol (161715-27-1) → (+)-(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-{[1-(2-thiazolin-2-yl)-3-azetidinyl]mercapto}-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid p-nitrobenzyl ester (161715-20-4)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: 93 percent / DMAP; Et3N / tetrahydrofuran / 0.5 h / 5 °C 2.1: 88 percent / potassium thioacetate / dimethylformamide / 5.5 h / 100 °C 3.1: KOH / propan-2-ol; methanol / 0.17 h / 5 °C 3.2: 87 percent / HCl / propan-2-ol; methanol / 15 h / 5 °C 4.1: 94 percent / diisopropyl ethylamine; MeCN / 2 h / -20 °C View Scheme

3-acetylthio-1-(1,3-thiazolin-2-yl)azetidine (161715-28-2) → (+)-(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-{[1-(2-thiazolin-2-yl)-3-azetidinyl]mercapto}-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid p-nitrobenzyl ester (161715-20-4)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: KOH / propan-2-ol; methanol / 0.17 h / 5 °C 1.2: 87 percent / HCl / propan-2-ol; methanol / 15 h / 5 °C 2.1: 94 percent / diisopropyl ethylamine; MeCN / 2 h / -20 °C View Scheme

(+)-(4R,5R,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-(diphenylphosphoryloxy)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid p-nitrobenzyl ester + 1-(4,5-dihydro-1,3-thiazol-2-yl)-3-mercaptoazetidine hydrochloride → (+)-(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-{[1-(2-thiazolin-2-yl)-3-azetidinyl]mercapto}-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid p-nitrobenzyl ester (161715-20-4)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetonitrile at 0℃; for 4h;

(+)-(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-{[1-(2-thiazolin-2-yl)-3-azetidinyl]mercapto}-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid p-nitrobenzyl ester (161715-20-4) → (4R,5S,6S)-3-{[1-(4,5-dihydro-1,3-thiazol-2-yl)azetidin-3-yl]sulfanyl}-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid (161715-21-5)

Conditions	Yield
With hydrogen In water; butan-1-ol at 20℃; under 15001.5 Torr; for 4h; Solvent; Pressure; Reagent/catalyst;	94.5%
With 0.5% Pd/C; hydrogen; sodium hydrogencarbonate In water; butan-1-ol at 25 - 30℃; under 7500.75 Torr; for 3h; Reagent/catalyst;	89.3%
With sodium hydrogencarbonate; palladium on activated charcoal In water; butan-1-ol at 20℃; under 3000.24 Torr; for 1.5h;	82%

(+)-(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-{[1-(2-thiazolin-2-yl)-3-azetidinyl]mercapto}-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid p-nitrobenzyl ester (161715-20-4) → 3-[1-(4,5-dihydro-thiazol-2-yl)-azetidin-3-ylsulfanyl]-6-(1-hydroxy-ethyl)-4-methyl-7-oxo-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 5-methyl-2-oxo-[1,3]dioxol-4-ylmethyl ester

Conditions	Yield
Multi-step reaction with 2 steps 1: 82 percent / sodium hydrogen carbonate / Pd-C / butan-1-ol; H2O / 1.5 h / 20 °C / 3000.24 Torr 2: 54 percent / benzyltriethylammonium chloride; diisopropylethylamine / dimethylformamide / 4 h / 45 °C View Scheme

(+)-(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-{[1-(2-thiazolin-2-yl)-3-azetidinyl]mercapto}-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid p-nitrobenzyl ester (161715-20-4) → 3-[1-(4,5-dihydro-thiazol-2-yl)-azetidin-3-ylsulfanyl]-6-(1-hydroxy-ethyl)-4-methyl-7-oxo-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 3-oxo-1,3-dihydro-isobenzofuran-1-yl ester

Conditions	Yield
Multi-step reaction with 2 steps 1: 82 percent / sodium hydrogen carbonate / Pd-C / butan-1-ol; H2O / 1.5 h / 20 °C / 3000.24 Torr 2: 84 percent / benzyltriethylammonium chloride; diisopropylethylamine / dimethylformamide / 4 h / 45 °C View Scheme

(+)-(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-{[1-(2-thiazolin-2-yl)-3-azetidinyl]mercapto}-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid p-nitrobenzyl ester (161715-20-4) → 3-[1-(4,5-dihydro-thiazol-2-yl)-azetidin-3-ylsulfanyl]-6-(1-hydroxy-ethyl)-4-methyl-7-oxo-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-methyl-benzoyloxymethyl ester

Conditions	Yield
Multi-step reaction with 2 steps 1: 82 percent / sodium hydrogen carbonate / Pd-C / butan-1-ol; H2O / 1.5 h / 20 °C / 3000.24 Torr 2: 84 percent / benzyltriethylammonium chloride; diisopropylethylamine / dimethylformamide / 4 h / 45 °C View Scheme

(+)-(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-{[1-(2-thiazolin-2-yl)-3-azetidinyl]mercapto}-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid p-nitrobenzyl ester (161715-20-4) → 3-[1-(4,5-dihydro-thiazol-2-yl)-azetidin-3-ylsulfanyl]-6-(1-hydroxy-ethyl)-4-methyl-7-oxo-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-chloro-benzoyloxymethyl ester

Conditions	Yield
Multi-step reaction with 2 steps 1: 82 percent / sodium hydrogen carbonate / Pd-C / butan-1-ol; H2O / 1.5 h / 20 °C / 3000.24 Torr 2: 81 percent / benzyltriethylammonium chloride; diisopropylethylamine / dimethylformamide / 4 h / 45 °C View Scheme

(+)-(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-{[1-(2-thiazolin-2-yl)-3-azetidinyl]mercapto}-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid p-nitrobenzyl ester (161715-20-4) → 3-[1-(4,5-dihydro-thiazol-2-yl)-azetidin-3-ylsulfanyl]-6-(1-hydroxy-ethyl)-4-methyl-7-oxo-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid cyclohexanecarbonyloxymethyl ester

Conditions	Yield
Multi-step reaction with 2 steps 1: 82 percent / sodium hydrogen carbonate / Pd-C / butan-1-ol; H2O / 1.5 h / 20 °C / 3000.24 Torr 2: 71 percent / benzyltriethylammonium chloride; diisopropylethylamine / dimethylformamide / 4 h / 45 °C View Scheme

(+)-(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-{[1-(2-thiazolin-2-yl)-3-azetidinyl]mercapto}-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid p-nitrobenzyl ester (161715-20-4) → 3-[1-(4,5-dihydro-thiazol-2-yl)-azetidin-3-ylsulfanyl]-6-(1-hydroxy-ethyl)-4-methyl-7-oxo-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 4-methyl-cyclohexanecarbonyloxymethyl ester

Conditions	Yield
Multi-step reaction with 2 steps 1: 82 percent / sodium hydrogen carbonate / Pd-C / butan-1-ol; H2O / 1.5 h / 20 °C / 3000.24 Torr 2: 80 percent / benzyltriethylammonium chloride; diisopropylethylamine / dimethylformamide / 4 h / 45 °C View Scheme

(+)-(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-{[1-(2-thiazolin-2-yl)-3-azetidinyl]mercapto}-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid p-nitrobenzyl ester (161715-20-4) → 3-[1-(4,5-dihydro-thiazol-2-yl)-azetidin-3-ylsulfanyl]-6-(1-hydroxy-ethyl)-4-methyl-7-oxo-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 1-cyclohexyloxycarbonyloxy-ethyl ester

Conditions	Yield
Multi-step reaction with 2 steps 1: 82 percent / sodium hydrogen carbonate / Pd-C / butan-1-ol; H2O / 1.5 h / 20 °C / 3000.24 Torr 2: 82 percent / benzyltriethylammonium chloride; diisopropylethylamine / dimethylformamide / 4 h / 45 °C View Scheme

(+)-(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-{[1-(2-thiazolin-2-yl)-3-azetidinyl]mercapto}-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid p-nitrobenzyl ester (161715-20-4) → 3-[1-(4,5-dihydro-thiazol-2-yl)-azetidin-3-ylsulfanyl]-6-(1-hydroxy-ethyl)-4-methyl-7-oxo-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid 1-methyl-cyclohexanecarbonyloxymethyl ester

Conditions	Yield
Multi-step reaction with 2 steps 1: 82 percent / sodium hydrogen carbonate / Pd-C / butan-1-ol; H2O / 1.5 h / 20 °C / 3000.24 Torr 2: 88 percent / benzyltriethylammonium chloride; diisopropylethylamine / dimethylformamide / 4 h / 45 °C View Scheme

(+)-(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-{[1-(2-thiazolin-2-yl)-3-azetidinyl]mercapto}-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid p-nitrobenzyl ester (161715-20-4) → 3-[1-(4,5-dihydro-thiazol-2-yl)-azetidin-3-ylsulfanyl]-6-(1-hydroxy-ethyl)-4-methyl-7-oxo-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylic acid cyclohexylacetoxymethyl ester

Conditions	Yield
Multi-step reaction with 2 steps 1: 82 percent / sodium hydrogen carbonate / Pd-C / butan-1-ol; H2O / 1.5 h / 20 °C / 3000.24 Torr 2: 76 percent / benzyltriethylammonium chloride; diisopropylethylamine / dimethylformamide / 4 h / 45 °C View Scheme

(+)-(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-{[1-(2-thiazolin-2-yl)-3-azetidinyl]mercapto}-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid p-nitrobenzyl ester (161715-20-4) → L-084

Conditions	Yield
Multi-step reaction with 2 steps 1: 82 percent / sodium hydrogen carbonate / Pd-C / butan-1-ol; H2O / 1.5 h / 20 °C / 3000.24 Torr 2: 78 percent / benzyltriethylammonium chloride; diisopropylethylamine / dimethylformamide / 4 h / 45 °C View Scheme
Multi-step reaction with 3 steps 1.1: 0.5% Pd/C; sodium hydrogencarbonate; hydrogen / butan-1-ol; water / 3 h / 25 - 30 °C / 7500.75 Torr 2.1: N-benzyl-N,N,N-triethylammonium chloride; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1 h / 35 °C 2.2: 7 - 8 °C 3.1: sodium hydrogencarbonate / water; ethyl acetate / 2.5 h View Scheme

(+)-(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-{[1-(2-thiazolin-2-yl)-3-azetidinyl]mercapto}-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid p-nitrobenzyl ester (161715-20-4) → C22H31N3O6S2*ClH

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 0.5% Pd/C; sodium hydrogencarbonate; hydrogen / butan-1-ol; water / 3 h / 25 - 30 °C / 7500.75 Torr 2.1: N-benzyl-N,N,N-triethylammonium chloride; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 1 h / 35 °C 2.2: 7 - 8 °C View Scheme

Upstream product

• 179337-57-6 1-(4,5-dihydro-1,3-thiazol-2-yl)-3-mercaptoazetidine hydrochloride 
• 161715-28-2 3-acetylthio-1-(1,3-thiazolin-2-yl)azetidine 
• 161715-27-1 1-(1,3-thiazolin-2-yl-)azetidin-3-ol 
• 179337-62-3 3-methanesulfonyloxy-1-(1,3-thiazolin-2-yl)azetidine 
• 93711-81-0 (4-nitrophenyl)methyl (4R,5R,6S)-3-[(diphenoxyphosphinyl)oxy]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate 

Downstream Products

• 161715-24-8 tebipenem 
• 161715-21-5 Tebipenem 

Relevant articles and documents

Syntheses and pharmacokinetic studies of prodrug esters for the development of oral carbapenem, L-084

We discovered an orally active carbapenem, L-084, through pharmacokinetic studies on various prodrug esters of (1R,5S,6S)-6-[(R)-1-hydroxyethyl]-1-methyl- 2-[1-(1,3-thiazolin-2-yl)azetidin-3-yl]thio-1-carbapen-2-em-3-carboxylic acid (LJC11,036). L-084 showed a strong antimicrobial activity against Gram-positive and Gram-negative bacteria and exhibited the highest intestinal absorption among synthesized prodrugs of LJC11,036. Japan Antibiotics Research Association.

Preparation method of medicinal tebipenem pivoxil

The invention discloses a preparation method of medicinal tebipenem pivoxil, which comprises the following steps: taking MAP and YKTP-1 as raw materials, sequentially carrying out condensation, reduction and substitution reaction, and purifying the material after the substitution reaction twice to obtain the medicinal tebipenem pivoxil. A primary purification process comprises the following steps: adding ethyl acetate into the material after the substitution reaction, conducting filtering, adding water into the filtrate, adjusting the pH value, carrying out liquid separation to obtain a water layer, adjusting the pH value of the water layer, conducting extracting with ethyl acetate to obtain an organic layer, washing the organic layer, conducting drying, decolorizing and filtering, carrying out vacuum concentration on the filtrate, conducting crystallizing and centrifuging, leaching a filter cake with ethyl acetate, and conducting drying in vacuum to obtain YKTP-4; and a secondary purification process comprises the following steps: mixing YKTP-4 with ethyl acetate, adding activated carbon, conducting stirring, conducting filtering to obtain filtrate, concentrating the filtrate to YKTP-4 under reduced pressure, conducting crystallizing and centrifuging, leaching a filter cake with ethyl acetate, and performing vacuum drying to obtain the medicinal tebipenem pivoxil.

Preparation method of high-purity tebipenem pivoxil crystals

The invention discloses a preparation method of high-purity tebipenem pivoxil crystals. The method comprises the following steps: adding a first solvent to crude tebipenem pivoxil, and performing stirring to obtain a primary dissolved product; adding a second solvent dropwise to the primary dissolved product at a reaction temperature, and then performing stirring for crystallization, wherein the first solvent contains water; the second solvent is acetonitrile; the reaction temperature is 0-60 DEG C. The tebipenem pivoxil crystals with high purity and low solvent residue content can be preparedwith the method.

Preparation method of tebipenem pivoxil

The invention provides a preparation method of tebipenem pivoxil, and relates to the technical field of pesticide synthesis. The preparation method of the tebipenem pivoxil comprises the following steps that 1-(4,5-dihydro-2-thiazolyl) azetidine-3-thiol hydrochloride and 1 beta-methyl vinyl phosphate are used as raw materials to take a reaction under the existence of diisopropylethylamine, and an acetonitrile water solution is used for washing to obtain an intermediate I; the intermediate I, an n-butyl alcohol water solution, a palladium-carbon catalyst and sodium bicarbonate take a mixed reaction, and treatment is performed to obtain an intermediate II; the intermediate II and chloromethyl pivalate take a reaction through phase transfer catalyst catalysis under the existence of diisopropylethylamine and dimethylformamide to obtain an intermediate III; the intermediate III and a sodium bicarbonate water solution are mixed, ethyl acetate is added, and reaction and refining are performed to prepare the tebipenem pivoxil. The preparation method has the advantages that the purity and the yield of the intermediates are obviously improved; the purity of the final product of the tebipenem pivoxil reaches 99.21 to 99.78 percent; the yield reaches 88.7 to 92.1 percent.