potassium;2-ethylhexanoate

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

Procedure: To a solution of 117 mg of allyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(imidazo[5,1-b]thiazol-7-yl)-1-methyl-1-carbapen-2-em-3-carboxylate in a mixed solvent of 2.5 ml of dichloromethane and 2.5 ml of ethy acetate were added 8.1 mg of triphenylphosphine, 56.5 mg of potassium 2-ethylhexanoate, and 11.8 mg of tetrakis(triphenylphosphine)palladium (0), and the mixture was stirred under the atmosphere of argon at room temperature for 20 minutes. After confirming the exhaustion of the starting materials, the reaction mixture was diluted with 10 ml of ethyl acetate, extracted three or four times with water, and the aqueous layer was concentrated under reduced pressure. The concentrate was purified by column chromatography on COSMOSEAL 40C18-PREP to give the title compound in a yield of 55 mg. extracted three or four times with water the aqueous layer was concentrated under reduced pressure The concentrate was purified by column chromatography on COSMOSEAL 40C18-PREP

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

Procedure: To a solution of 40 mg of allyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(imidazo[5,1-b]thiazol-5-yl)-1-methyl-1-carbapen-2-em-3-carboxylate in 0.8 ml of dichloromethane and 0.8 ml of ethyl acetate were added under the atmosphere of argon 3.4 mg of triphenylphosphine, 29 mg of potassium 2-ethylhexanoate, 6.4 mg of tetrakis-triphenylphosphine palladium (0), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was poured into diethyl ether, and the resulting precipitate was collected by filtration, and purified by column chromatography on COSMOSEAL 40C18-PREP (water:methanol=20:1) to give 13 mg of the title compound. the resulting precipitate was collected by filtration purified by column chromatography on COSMOSEAL 40C18-PREP (water:methanol=20:1)

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

Procedure: N,N'-diisopropylethylenediammonium diclavulanate (10 g, clavulanic acid content 69%) was dissolved in water (10 ml), the solution was diluted with isopropanol (190 ml) and a solution (15 ml, 2M) of potassium 2-ethylhexanoate in isopropanol was added within 15 min. with stirring. The obtained suspension was stirred for another 30 min. whereat a precipitate separated, which was filtered off, washed with isopropanol and then dried. Thus there was obtained potassium clavulanate (4.8 g; 70%), (USP Grade, clavulanic acid content 81% as determined by the HPLC method). The obtained suspension was stirred for another 30 min. whereat a precipitate separated which was filtered off washed with isopropanol dried

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

Procedure: A solution of allyl (5R,6S)-2-azido-6-[(R)-1-hydroxyethyl]carbapen-2-em-3-carboxylate (42 mg, 0.15 mmol) and triphenylphosphine (12 mg, 0.045 mmol) in 1:1 methylene chloride-ethyl acetate (2.7 ml) is treated with 0.5M potassium 2-ethylhexanoate in ethyl acetate (0.3 ml, 0.15 mmol) and tetrakis(triphenylphosphine)palladium (O) (13.8 mg, 0.012 mmol). The mixture is stirred 15 minutes at ambient temperature under a nitrogen atmosphere, diluted with diethyl ether, and centrifuged. The insoluble pellet is washed with ether and dried under vacuum to afford potassium (5R,6S)-2-azido-6-[(R)-1-hydroxyethyl]-carbapen-2-em-3-carboxylate. The insoluble pellet is washed with ether dried under vacuum

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

Procedure: N,N'-diisopropylethylenediammonium diclavulanate (10 g, clavulanic acid content 69%) was dissolved in water (10 ml), the solution was diluted with isopropanol (190 ml) and a solution (15 ml, 2M) of potassium 2-ethylhexanoate in isopropanol was added within 15 min. with stirring. The obtained suspension was stirred for another 30 min. whereat a precipitate separated, which was filtered off, washed with isopropanol and then dried. Thus there was obtained potassium clavulanate (4.8 g; 70%), (USP Grade, clavulanic acid content 81% as determined by the HPLC method). The obtained suspension was stirred for another 30 min. whereat a precipitate separated which was filtered off washed with isopropanol dried

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

Procedure: To a solution of 3-methoxyiminomethyl-7β-(2-thienylacetamido)-3-cephem-4-carboxylic acid (10.1 g) in ethyl acetate (50 ml) is added a solution of potassium 2-ethylhexanoate (4.5 g) in propanol (8.9 ml), and the mixture is kept in a refrigerator for 15 hours. The crystals formed are collected by filtration, washed with ethyl acetate, and recrystallized from a mixture of methanol and ether to give potassium 3-methoxyiminomethyl-7β-(2-thienylacetamido)-3-cephem-4-carboxylate monohydrate (10.5 g). m.p. 206°-209° C. Yield: 91%. The crystals formed are collected by filtration washed with ethyl acetate recrystallized from a mixture of methanol and ether

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

Procedure: A solution of allyl (5R,6S)-2-azido-6-[(R)-1-hydroxyethyl]carbapen-2-em-3-carboxylate (42 mg, 0.15 mmol) and triphenylphosphine (12 mg, 0.045 mmol) in 1:1 methylene chloride-ethyl acetate (2.7 ml) is treated with 0.5M potassium 2-ethylhexanoate in ethyl acetate (0.3 ml, 0.15 mmol) and tetrakis(triphenylphosphine)palladium (0) (13.8 mg, 0.012 mmol). The mixture is stirred 15 minutes at ambient temperature under a nitrogen atmosphere, diluted with diethyl ether, and centrifuged. The insoluble pellet is washed with ether and dried under vacuum to afford potassium (5R,6S)-2-azido-6-[(R)-1-hydroxyethyl]-carbapen-2-em-3-carboxylate. The insoluble pellet is washed with ether dried under vacuum

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

Procedure: A solution of allyl (5R,6S)-2-azido-6-[(R)-1-hydroxyethyl]carbapen-2-em-3-carboxylate (42 mg, 0.15 mmol) and triphenylphosphine (12 mg, 0.045 mmol) in 1:1 methylene chloride-ethyl acetate (2.7 ml) is treated with 0.5M potassium 2-ethylhexanoate in ethyl acetate (0.3 ml, 0.15 mmol) and tetrakis(triphenylphosphine)palladium (0) (13.8 mg, 0.012 mmol). The mixture is stirred 15 minutes at ambient temperature under a nitrogen atmosphere, diluted with diethyl ether, and centrifuged. The insoluble pellet is washed with ether and dried under vacuum to afford potassium (5R,6S)-2-azido-6-[(R)-1-hydroxyethyl]-carbapen-2-em-3-carboxylate. The insoluble pellet is washed with ether dried under vacuum

Conditions: temp:12.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Hydroquinone (10 g, 0.09 mol) and 1,2-dichloroethane (30 mL) was taken in a round bottom flask, after cooling the flask to about 10-15° C., sulfuric acid (36 N, 8.9 g) was added dropwise at the same temperature and stirring continued further for about 10-15 min. Temperature was slowly raised to 40° C. then stirred for 3-8 h. The reaction mass was then cooled to 25-35° C. and ethyl acetate (100 mL) added to dissolve the solid formed. A solution of potassium 2-ethylhexanoate (18.2 g, 0.099 mol) in ethyl acetate (100 mL) was added slowly. The reaction was further stirred for an hour. The precipitated crude solid was filtered, washed with ethyl acetate to give 18 g of 2,5-dihydroxybenzenesulfonic acid potassium salt. Temperature was slowly raised to 40° C. then stirred for 3-8 h The reaction mass was then cooled to 25-35° C. to dissolve the solid formed The reaction was further stirred for an hour The precipitated crude solid was filtered washed with ethyl acetate

Conditions: temp:12.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Hydroquinone (10 g, 0.09 mol) and dichloromethane (30 mL), was taken in a round bottom flask, after cooling the flask to about 10-15° C., sulfuric acid (36 N, 8.9 g) was added dropwise at the same temperature and stirring continued further for about 10-15 min. Temperature was slowly raised to 30-40° C. then stirred for 1-2 h. The reaction mass was then cooled to 25-35° C. and ethyl acetate (100 mL) added to dissolve the solid formed. A solution of potassium 2-ethylhexanoate (18.2 g, 0.099 mol) in ethyl acetate (100 mL) was added slowly. The reaction was further stirred for an hour. The precipitated crude solid was filtered, washed with ethyl acetate to give 16 g of 2,5-dihydroxybenzenesulfonic acid potassium salt. Temperature was slowly raised to 30-40° C. then stirred for 1-2 h The reaction mass was then cooled to 25-35° C. to dissolve the solid formed The reaction was further stirred for an hour The precipitated crude solid was filtered washed with ethyl acetate

Conditions: temp:12.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Hydroquinone (10 g, 0.09 mol) was taken in a round bottom flask, after cooling the flask to about 10-15° C., sulfuric acid (36 N, 8.9 g) was added dropwise at the same temperature and stirring continued further for about 10-15 min. Temperature was slowly raised to 50-60° C. then stirred for 3-8 h. The reaction mass was then cooled to 25-35° C. and ethyl acetate (100 mL) added to dissolve the solid formed. A solution of potassium 2-ethylhexanoate (18.2 g, 0.099 mol) in ethyl acetate (100 mL) was added slowly. The reaction was further stirred for an hour. The precipitated crude solid was filtered, washed with ethyl acetate to give 16 g of 2,5-dihydroxybenzenesulfonic acid potassium salt. Temperature was slowly raised to 50-60° C. then stirred for 3-8 h The reaction mass was then cooled to 25-35° C. to dissolve the solid formed The reaction was further stirred for an hour The precipitated crude solid was filtered washed with ethyl acetate

Conditions: temp:12.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Hydroquinone (10 g, 0.09 mol) was taken in a round bottom flask, after cooling the flask to about 10-15° C., sulfuric acid (36 N, 8.9 g) was added dropwise at the same temperature and stirring continued further for about 10-15 min. Temperature was slowly raised to 50-60° C. then stirred for 3-8 h. The reaction mass was then cooled to 25-35° C. and ethyl acetate (100 mL) added to dissolve the solid formed. A solution of potassium 2-ethylhexanoate (18.2 g, 0.099 mol) in ethyl acetate (100 mL) was added slowly. The reaction was further stirred for an hour. The precipitated crude solid was filtered, washed with ethyl acetate to give 16 g of 2,5-dihydroxybenzenesulfonic acid potassium salt. Temperature was slowly raised to 50-60° C. then stirred for 3-8 h The reaction mass was then cooled to 25-35° C. to dissolve the solid formed The reaction was further stirred for an hour The precipitated crude solid was filtered washed with ethyl acetate