iodomethyl 2-methylpropanoate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In the same manner as described in Example 48, (1R, 5S, 6S)-2-[(3S)-pyrrolidine-2-thion-3-ylthio]-6-[(1R)-1-hydroxyethyl]-1-met hylcarbapen-2em-3-carboxylic acid potassium salt is treated with isobutyryloxymethyl iodide to give (1R, 5S, 6S)-2-[(3S)-pyrrolidine-2-thion-3-ylthio]-6-[(1R)-1-hydroxyethy l]-1-methylcarbapen-2-em-3-carboxylic acid isobutyryloxymethyl ester. hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In the same manner as described in Example 48, (1R, 5S, 6S)-2-[(3S)-pyrrolidine-2-thion-3-ylthio]-6-[(1R)-1-hydroxyethyl]-1-met hylcarbapen-2em-3-carboxylic acid potassium salt is treated with isobutyryloxymethyl iodide to give (1R, 5S, 6S)-2-[(3S)-pyrrolidine-2-thion-3-ylthio]-6-[(1R)-1-hydroxyethy l]-1-methylcarbapen-2-em-3-carboxylic acid isobutyryloxymethyl ester. hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In the same manner as described in Example 48, (1R, 5S, 6S)-2-[(3S)-pyrrolidine-2-thion-3-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid potassium salt is treated with isobutyryloxymethyl iodide to give (1R, 5S, 6S)-2-[(3S)-pyrrolidine-2-thion-3-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid isobutyryloxymethyl ester.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In the same manner as described in Example 48, (1R, 5S, 6S)-2-[(3S)-pyrrolidine-2-thion-3-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid potassium salt is treated with isobutyryloxymethyl iodide to give (1R, 5S, 6S)-2-[(3S)-pyrrolidine-2-thion-3-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid isobutyryloxymethyl ester.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (1R, 5S, 6S)-2-[(3R)-Pyrrolidine-2-thion-3-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid potassium salt (0.5 g) is suspended in N,N-dimethylformamide (5 ml). To the suspension is added isobutyryloxymethyl iodide (338 mg) under ice cooling, and the mixture is stirred at the same temperature for 30 minutes. To the reaction mixture is added ethyl acetate, and the mixture is washed with water, dried and concentrated to dryness under reduced pressure. The residue is purified by silica gel flash column chromatography (eluent, chloroform:methanol=20:1) to give (1R, 5S, 6S)-2-[(3R)-pyrrolidine-2-thion-3-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid isobutyryloxymethyl ester (0.14 g) as an amorphous powder. the mixture is washed with water dried concentrated to dryness under reduced pressure The residue is purified by silica gel flash column chromatography (eluent, chloroform:methanol=20:1)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of (1R, 5S, 6S)-2-[(4R)-pyrrolidine-2- thion-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methylcarbapen-2- em-3-carboxylic acid potassium salt (0.34 g), N,N-dimethylformamide (3 ml) and potassium carbonate (0.12 g) is added dropwise isobutyryloxymethyl iodide (0.27 g) under ice cooling. After stirring the mixture at the same temperature for 30 minutes, ethyl acetate (10 ml) is added to the reaction mixture, and the mixture is washed with water, and the organic layer is dried and evaporated under reduced pressure to remove the solvent. The residue is purified by silica gel flash column chromatography (eluent, chloroform: ethanol=20:1), followed by crystallization from isopropyl ether and ethyl acetate to give (1R, 5S, 6S)-2-[(4R)-pyrrolidine-2-thion-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid isobutyryloxymethyl ester (0.12 g) as colorless needles. the mixture is washed with water the organic layer is dried evaporated under reduced pressure to remove the solvent The residue is purified by silica gel flash column chromatography (eluent, chloroform: ethanol=20:1) followed by crystallization from isopropyl ether and ethyl acetate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of (1R, 5S, 6S)-2-[(4R)-pyrrolidine-2- thion-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methylcarbapen-2- em-3-carboxylic acid potassium salt (0.34 g), N,N-dimethylformamide (3 ml) and potassium carbonate (0.12 g) is added dropwise isobutyryloxymethyl iodide (0.27 g) under ice cooling. After stirring the mixture at the same temperature for 30 minutes, ethyl acetate (10 ml) is added to the reaction mixture, and the mixture is washed with water, and the organic layer is dried and evaporated under reduced pressure to remove the solvent. The residue is purified by silica gel flash column chromatography (eluent, chloroform: ethanol=20:1), followed by crystallization from isopropyl ether and ethyl acetate to give (1R, 5S, 6S)-2-[(4R)-pyrrolidine-2-thion-4-ylthio]-6-[(1R)-1-hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid isobutyryloxymethyl ester (0.12 g) as colorless needles. the mixture is washed with water the organic layer is dried evaporated under reduced pressure to remove the solvent The residue is purified by silica gel flash column chromatography (eluent, chloroform: ethanol=20:1) followed by crystallization from isopropyl ether and ethyl acetate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In the same manner as described in Example 48, (1R, 5S, 6S)-2-[(3S)-pyrrolidine-2-thion-3-ylthio]-6-[(1R)-1-hydroxyethyl]-1-met hylcarbapen-2em-3-carboxylic acid potassium salt is treated with isobutyryloxymethyl iodide to give (1R, 5S, 6S)-2-[(3S)-pyrrolidine-2-thion-3-ylthio]-6-[(1R)-1-hydroxyethy l]-1-methylcarbapen-2-em-3-carboxylic acid isobutyryloxymethyl ester. hydroxyethyl]-1-methylcarbapen-2-em-3-carboxylic acid

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In the same manner as in Example 81, 360 mg of the title compound was prepared from 325 mg of sodium (1R,5S,6S)-6-((1R)-1-hydroxyethyl)-2-[[(Z)-2-(4-hydroxymethylthiazol-5-yl)ethen-1-yl]thio]-1-methyl-1-carbapen-2-em-3-carboxylate and 220 mg of isobutyryloxymethyl iodide.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In the same manner as in Example 81, 360 mg of the title compound was prepared from 325 mg of sodium (1R,5S,6S)-6-((1R)-1-hydroxyethyl)-2-[[(Z)-2-(4-hydroxymethylthiazol-5-yl)ethen-1-yl]thio]-1-methyl-1-carbapen-2-em-3-carboxylate and 220 mg of isobutyryloxymethyl iodide.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In the same manner as in Example 81, 360 mg of the title compound was prepared from 325 mg of sodium (1R,5S,6S)-6-((1R)-1-hydroxyethyl)-2-[[(Z)-2-(4-hydroxymethylthiazol-5-yl)ethen-1-yl]thio]-1-methyl-1-carbapen-2-em-3-carboxylate and 220 mg of isobutyryloxymethyl iodide.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In the same manner as Example 8, 7-[2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylic acid (syn-isomer) was reacted with iodomethyl isobutyrate in the presence of triethylamine to give isobutyryloxymethyl 7-[2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylate (syn-isomer), mp 95°-100° C. (decompn.).