Abstract: The present invention relates to a method for crystallization of (2R)-2-{(3S,4S)-3-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-2-oxoazetidin-4-yl}propionic acid, and is characterized in that crystallization is carried out by mixing a solution containing the compound with a substituted aromatic hydrocarbon solvent and/or a halogenated hydrocarbon solvent. The method can provide a crystal of the compound with a high purity and a high yield while the content of 2S isomer is kept at a low level.

Abstract: An improved crystallization method for an azetidinone compound represented by the formula 1: , which is extremely useful as a common intermediate for the synthesis of 1?-methylcarbapenem compounds. The present method provides crystals having higher quality and stability than conventional crystals and excellent filterability at the time of recovery; and an azetidinone compound having a low content of impurity, and which has a controlled particle size distribution of crystals and improved handleability and stability. The crystallization is carried out by adding a hydrocarbon solvent to a solution in which an azetidinone compound extremely useful as a common intermediate for the synthesis of 1?-methylcarbapenem compounds is dissolved in the presence of a seed crystal in an amount of 200% by weight or less based on the weight of the azetidinone compound.

Abstract: The present invention relates to a method for crystallization of (2R)-2-{(3S, 4S)-3-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-2-oxoazetidin-4-yl}propionic acid, and is characterized in that crystallization is carried out by mixing a solution containing the compound with a substituted aromatic hydrocarbon solvent and/or a halogenated hydrocarbon solvent. The method can provide a crystal of the compound with a high purity and a high yield while the content of 2S isomer is kept at a low level.

Abstract: The present invention has its object to provide an easy process for producing (4R,5S,6S)-3-[[(3S,5S)-5-(dimethylaminocarbonyl)-3-pyrrolidinyl]thio]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid, excellent in antimicrobial activity. The present invention relates to a process for continuously producing (4R,5S,6S)-3-[[(3S,5S)-5-(dimethylaminocarbonyl)-3-pyrrolidinyl]thio]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid without isolating/purifying the reaction intermediate.

Abstract: The present invention provides a novel intermediate represented by formula (1), (3), or (4) for efficiently producing a 1?-methylcarbapenem compound for oral administration, and a process for producing the intermediate. That is, the present invention provides a process for producing a novel ?-lactam compound represented by formula (4), the process including allowing a ?-lactam compound represented by formula (5) as a starting material to react with a compound represented by formula (6) in the presence of a base to obtain a novel ?-lactam compound represented by formula (1), protecting the hydroxyl group, subsequently performing cyclization in the presence of a strong base, allowing the cyclized compound to react with diphenylphosphoryl chloride to obtain a novel ?-lactam compound represented by formula (3), and eliminating the protecting group therefrom.

Abstract: The present invention relates to an azetidinone compound extremely useful as a common intermediate for the synthesis of 1?-methylcarbapenem compounds. The present invention provides a crystallization method to obtain a crystal which has a higher quality and a higher stability than a conventional crystal and is excellent in filterability at the time of recovering crystal; an azetidinone compound having a low content of impurity; and an azetidinone compound which has a controlled particle size distribution of crystals and improved handleability and stability. The crystallization is carried out by adding a hydrocarbon solvent to a solution in which an azetidinone compound extremely useful as a common intermediate for the synthesis of 1?-methylcarbapenem compounds is dissolved in the presence of a seed crystal in an amount of 200% by weight or less based on the weight of the azetidinone compound.

Abstract: The present invention provides a process for efficiently producing a 1?-methylcarbapenem compound for oral administration. The process, which is for producing a 1?-methylcarbapenem compound represented by general formula (2), is characterized by reacting a ?-lactam compound represented by general formula (1) as a starting material with a thiol compound (R3—SH) in the presence of a base and optionally eliminating the protective group R1. In the formulae (1) and (2), R1 denotes a hydrogen atom, a trimethylsilyl group or a triethylsilyl group; R2 denotes an alkyl group having 1 to 10 carbon atoms or a cycloalkyl group having 3 to 10 carbon atoms; R3 denotes an organic group; and R4 denotes hydrogen, a trimethylsilyl group or a triethylsilyl group.

Abstract: The present invention provides a novel intermediate for efficiently producing a 1?-methylcarbapenem compound for oral administration, and a process for producing the intermediate. That is, the present invention provides a process for producing a novel ?-lactam compound represented by general formula (4), the process including allowing a lactam compound represented by general formula (5) as a starting material to react with a compound represented by general formula (6) in the presence of a base to obtain a novel ?-lactam compound represented by general formula (1), protecting the hydroxyl group, subsequently performing cyclization in the presence of a strong base, allowing the cyclized compound to react with diphenylphosphoryl chloride to obtain a novel ?-lactam compound represented by general formula (3), and eliminating the protecting group therefrom.

Abstract: The present invention provides a process for efficiently producing a 1?-methylcarbapenem compound for oral administration. The process, which is for producing a 1?-methylcarbapenem compound represented by general formula (2), is characterized by reacting a ?-lactam compound represented by general formula (1) as a starting material with a thiol compound (R3—SH) in the presence of a base and optionally eliminating the protective group R1. In the formulae (1) and (2), R1 denotes a hydrogen atom, a trimethylsilyl group or a triethylsilyl group; R2 denotes an alkyl group having 1 to 10 carbon atoms or a cycloalkyl group having 3 to 10 carbon atoms; R3 denotes an organic group; and R4 denotes hydrogen, a trimethylsilyl group or a triethylsilyl group.