151072-00-3

Usage

Uses

Used in Organic Synthesis:
(2S,4S)-5-p-nitrobenzyloxycarbonyl-2-thia-5-azabicyclo<2.2.1>heptan-3-one is used as a building block in organic synthesis for the creation of various complex molecules and compounds.
Used in Medicinal Chemistry Research:
In the field of medicinal chemistry, (2S,4S)-5-p-nitrobenzyloxycarbonyl-2-thia-5-azabicyclo<2.2.1>heptan-3-one is used as an intermediate for the preparation of pharmaceuticals and bioactive compounds, contributing to the development of new drugs and therapies.
Used in Pharmaceutical Industry:
(2S,4S)-5-p-nitrobenzyloxycarbonyl-2-thia-5-azabicyclo<2.2.1>heptan-3-one is used as a key intermediate in the pharmaceutical industry for the synthesis of drugs with potential therapeutic applications.
Used in Bioactive Compounds Synthesis:
(2S,4S)-5-p-nitrobenzyloxycarbonyl-2-thia-5-azabicyclo<2.2.1>heptan-3-one is also utilized in the synthesis of bioactive compounds, which have the potential to interact with biological systems and may be used for various therapeutic or diagnostic purposes.

Upstream product

• 51-35-4 4R-4-hydroxyproline 
• 4457-32-3 4-nitrobenzyl chloroformate 
• 96034-57-0 (2S,4R)-4-Hydroxy-1-(4-nitrobenzyloxycarbonyl)pyrrolidine-2-carboxylic acid 
• 151071-99-7 (2S,4R)-1-p-nitrobenzyloxycarbonyl-4-methanesulfonyloxy-2-pyrrolidinethiocarboxylic acid 

Downstream Products

• 138508-10-8 1-<(2S,4S)-4-mercapto-1-p-nitrobenzyloxycarbonyl-2-pyrrolidinylcarbonyl>-4-methylpiperidine 
• 96034-64-9 (2S,4S)-1-p-nitrobenzyloxycarbonyl-2-dimethylaminocarbonyl-4-thiolpyrrolidine 
• 127966-47-6 (2S,4S)-1-p-nitrobenzyloxycarbonyl-2-carboxy-4-mercaptopyrrolidine 
• 1206708-72-6 C₂₂H₂₉N₅O₆S₂ 
• 1350538-24-7 (2S,4S)-2-[(4-aminosulfonylphen-1-yl)iminomethylformyl]-4-thiol-1-(p-nitrobenzyloxycarbonyl)pyrrolidine 
• 1312953-83-5 (4R,5S,6S)-6-((R)-1-hydroxyethyl)-4-methyl-7-oxo-3-(((3S,5S)-5-((4-sulfamoylbenzyl)carbamoyl)pyrrolidin-3-yl)thio)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid 
• 1350538-25-8 (4R,5S,6S)-3-[[(3S,5S)-N-(4-nitrobenzyloxycarbonyl)-5-[(4-aminosulfonylphen-1-yl)methyl]carbamoyl]-3-pyrrolidinyl]thio-6-[(R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid (4-nitrobenzyl)methyl ester 
• 202467-69-4 (2S,4S)-2-[[(3-carboxyphenyl)amino]carbonyl]-4-mercapto-1-(4-nitrobenzyl)pyrrolidine carboxylate 

Relevant academic research and scientific papers

Method for synthesizing meropenem side chain intermediate thiol lactone by using sodium hydrosulfide

The invention relates to a method for synthesizing meropenem side chain intermediate thiol lactone by using sodium hydrosulfide. The thiol lactone is synthesized by performing carboxyl activation andhydroxyl activation on a reactant M1 and adding polyethylene glycol and sodium hydrosulfide through a one-pot method. The thiol lactone is synthesized by performing carboxyl activation and hydroxyl activation on the M1 and adding the PEG and NaHS through one-pot vulcanization and cyclization, the conversion rate of the M1 is obviously improved; the highest yield of the thiol lactone is 98.9 percent or higher; the purity reaches 97.4 percent or higher; reaction conditions are mild and safe. The adopted sodium hydrosulfide is stable in chemical property and easy to store; the synthesized thiol lactone is high in yield; the defects that sodium sulfide is easy to deliquesce and oxidize, high in toxicity, unstable in property, high in storage requirement and the like are overcome, environmentalpollution is reduced, the operation environment is safe, healthy work of experimenters is facilitated, the cost of personnel and equipment is reduced to a certain extent, and the method is suitable for green and efficient large-scale production of enterprises.

Preparation method of improved meropenem side chain intermediate thiol lactone by adding surfactant

The invention provides a preparation method of an improved meropenem side chain intermediate thiol lactone by adding a surfactant. The meropenem side chain intermediate is prepared by performing carboxyl activation and hydroxyl activation on M1 [(2S, 4R)-2-carboxyl-1-(4-nitrobenzyloxycarbonyl) pyrrolidine] and adding a cheap surfactant to vulcanize and form a ring by a one-pot method. The surfacetension of dichloromethane and water can be reduced by utilizing the surfactant, wherein the molar weight of the added surfactant is only 3-10% of the molar weight of M1, the highest yield of the obtained thiol lactone reaches 96.5% or above, the purity can reach 98.1% or above, the reaction temperature is increased by adding the surfactant, and when the temperature is controlled to be-16 DEG C to-15 DEG C, the thiol lactone can still be synthesized at a high yield, the surfactant source is wide, meanwhile, after a solvent and water are evaporated and removed, the surfactant can be recycled, so that the environmental pollution is reduced, and the industrial production of the thiol lactone is facilitated.

Preparation method of meropenem side chain intermediate mercaptan lactone

The invention provides a synthesis method of a meropenem side chain intermediate mercaptan lactone with the high yield. The synthesis method comprises the steps that (2S,4R)-2-carboxyl-1-(4-nitrobenzyloxycarbonyl)pyrrolidine) is added into dichloromethane, the liquid temperature is kept at minus 26 DEG C to minus 17 DEG C, isopropyl chlorocarbonate is dropwise added, and then triethylamine is dropwise added to activate carboxyl; MsCl is dropwise added under the same temperature condition, and then triethylamine is dropwise added to activate hydroxyl; a sodium sulfide nonahydrate, a phase transfer catalyst and water are dissolved into a solution, and the solution is added into a reaction solution under the same temperature condition; deionized water is added at 0 DEG C for liquid separation, and an organic phase is separated; the organic phase is subjected to a reflux reaction in a water bath kettle; and alkali is used for adjusting till pH is 8 to 9, an oil phase 1 is separated, the oil phase 1 continues to be adjusted through acid till pH is 1 to 2, an oil phase 2 is separated, after the oil phase 2 is subjected to decompression distillation, oily liquid is obtained, a crystallization solvent is added into the oily liquid, then a low-temperature reaction for bath cooling is conducted, and filtering is conducted to obtain the meropenem side chain intermediate mercaptan lactone.

A luer Ertapenem, luer he lateral chain and its preparation method

The invention discloses ertapenem and ertapenem side chains, as well as preparation methods of ertapenem and ertapenem side chains. L-hydroxyproline is protected by p-nitrobenzyl ester to obtain (2S,4R)-4-hydroxyl-1-(((4-Nitrobenzformyl)-oxyl)caboyl)pyrrolidine-2-carboxylic acid; then 4-nitro(1S,4S)-3-oxo-2-thia-5-azabicyclo[2.2.1]heptan-5-carboxylic anhydride can be obtained, and reacts with m-aminobenzoic acid p-nitrobenzyl ester to obtain ertapenem side chain III; and the ertapenem can be synthesized through two-step chemical reaction of condensation and deprotection to the ertapenem side chain III and a raw material MAP. An ertapenem side chain I (10), an ertapenem side chain II (13) and the ertapenem side chain III (2) which are prevailing in the market can be synthesized through simple steps, without the need of ultralow temperature, industrialization is easy, and the product purity is high, and the operation is simple and convenient.

Meropenem side chain intermediate and preparation method thereof

The invention relates to a meropenem side chain intermediate and a preparation method thereof. The preparation method is used for preparing a (1S, 4S)-5-p-nitrobenzyloxycarbonyl-2-thia-5-azabicyalo[2, 2, 1]heptan-3-one (shown in the formula and called as thiollactone for short). In a nitrogen protective atmosphere, (2S, 4R)-2-carboxyl-4-hydroxy-1-(4-nitrobenzyloxycarbonyl)pyrrolidine is added into dichloromethane, the mixture undergoes a carboxyl activation reaction, the reaction product undergoes a hydroxy acylation reaction, the reaction product undergoes a sulfuration cyclization reaction, the reaction product is subjected to reduced pressure distillation, a crystallization solvent is added into the distillation product, the product is cooled to a temperature of -5 to -10 DEG C and precipitates for 2h, and the crystals are filtered to form the (1S, 4S)-5-p-nitrobenzyloxycarbonyl-2-thia-5-azabicyalo[2, 2, 1]heptan-3-one (shown in the formula and called as thiollactone for short). The preparation method provides high purity thiollactone. A high-purity meropenem side chain can be prepared through thiollactone aminolysis. The preparation method utilizes mild reaction conditions, is safe, does not produce pollution on the environment and is suitable for industrial production. The thiollactone can be used for synthesis of an ertapenem side chain, a doripenem side chain and some amino-compounds, esters and ketones.

An Efficient Synthesis of (2S,4S)-2-Substituted-4-mercaptopyrrolidine Derivatives

An efficient synthesis of (2S,4S)-2-substituted 4-mercapto-1-p-nitrobenzyloxycarbonylpyrrolidine (2) was studied.Intramolecular cyclization of (2S,4R)-1-p-nitrobenzyloxycarbonyl-4-methanesulfonyloxy-2-pyrrolidinethiocarboxylic acid (8), derived from trans-4-hydroxy-L-proline (3), afforded (1S,4S)-5-p-nitrobenzyloxycarbonyl-2-thia-5-azabicycloheptan-3-one (7).Reaction of 7 with primary amine, secondary amine and alkoxide afforded corresponding 2 in high yield.

Pyrrolidine derivatives and process for preparing the same

Pyrrolidine derivatives of the formula (1): STR1 wherein R is a protective group of the amino group, intermediates for constructing the 2-positioned side chain of antibacterial penem and carbapenem compounds, are prepared by allowing STR2 to react with ac