sodium;2-ethylhexanoate

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

Procedure: A mixture of 7-chloro-1-ethyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid [J. Med. Chem., 23, 1358 (1980)] (0.52 g, 2 mmol) and 2-methylpiperazine (0.8 g, 8 mmol) was heated at 175° for 5 hours. The residue was dissolved in ethylacetate (10 mL) and chloroform (10 mL), and a solution of sodium-2-ethyl- hexanoate (0.33 g, 2 mmol) in ethyl acetate (20 mL) was added. The mixture was stirred for 30 minutes and the precipitate was collected. The crude product was purified by preparative liquid chromatography (C-18 reverse phase, gradient 0-40% acetonitrile in water) to give a pale yellow lyophilized solid (0.5 g, 75% yield). was heated at 175° for 5 hours the precipitate was collected The crude product was purified by preparative liquid chromatography (C-18 reverse phase, gradient 0-40% acetonitrile in water)

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

Procedure: To a suspension of 2-mercapto-4-pyridinecarboxylic acid (7.65 g) in a mixture of tetrahydrofuran (60 ml) and methanol (60 ml) was added a solution of sodium 2-ethylhexanoate in isopropyl alcohol (27.5%) and the mixture was stirred for 2 days at room temperature. The reaction mixture was evaporated and the residue was washed with a mixture of acetone and ethanol. The crystals were collected by filtration dried over phosphorus pentoxide to give disodium 2-sulfido-4-pyridinecarboxylate (8.5 g). The reaction mixture was evaporated the residue was washed with a mixture of acetone and ethanol The crystals were collected by filtration dried over phosphorus pentoxide

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

Procedure: A mixture of (3S,5R,6R)-6-amino-2,2-dimethylpenam-3-carboxylic acid (6ApA, 2.2056 g., 10.21 mmole), trimethyl chlorosilane (2.615 ml., 20.42 mmole), and triethylamine (2.84 ml., 20.3 mmole) in tetrahydrofuran, (50 ml.) was stirred for 1 hour at +20 to +25° and then cooled to -70°. To this solution at -70° was added a cold (-60 to -70°) solution of formic-acetic anhydride [generated by stirring formic acid (470 mg., 10.2 mmole), acetyl chloride (0.726 ml., 10.2 mmole) and triethylamine (1.42 ml., 10.2 mmole) at -60 to -70° in tetrahydrofuran (40 ml.). The solution contained suspended triethylamine hydrochloride] and triethylamine (1.42 ml., 10.2 mmole). The temperature of the mixture was allowed to rise to +20° over ca. 1 hour and the mixture was then filtered. The filtrate and washings were stirred and a solution of sodium 2-ethylhexanoate (2 g., 12 mmole) in tetrahydrofuran (2ml.) and ether (18 ml.) was added. The white precipitate was isolated by filtration, washed with ether and dried to give sodium (3S,5R,6R)-6-formamido-2,2-dimethylpenam-3-carboxylate as a white powder (1.6127 g., 6.06 mmole), 59.4%); m.p. 238° to 242° (dec.); [α]D + 281° (H2O); νmax. 3412 (NH), 1790 (azetidin-2-one), 1677 and 1505 (CONH), 1602 cm.-1 (CO2 -); τ 1.28 (1H, d, J 9 Hz, NH), 1.90 (1H, s, HCO), 4.40 to 4.60 (2H, m, C5 -H and C6 -H), 6.01 (1H, s, C3 -H), 8.42 (3H, s) and 8.50 (3H, s) (C[CH3 ]2). (Found : C, 40.7; H, 4.3; N, 10.3; Na, 8.6; S, 11.7. C9H11N2NaO4S (266.3) requires C, 40.5; H, 4.1; N, 10.5; Na, 8.6; S, 12.0%). cooled to -70° to rise to +20° over ca. 1 hour the mixture was then filtered The filtrate and washings were stirred The white precipitate was isolated by filtration washed with ether dried

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

Procedure: A solution of 120 g (3.0 moles) of sodium hydroxide was dissolved in 500 ml of distilled water. 2-Ethylhexanoic acid (475 g, 3.3 moles) was added with stirring to form sodium 2-ethylhexanoate. In a separate container, 200 g (0.5 mole) of chromium nitrate nonahydrate was dissolved in 500 ml of distilled water. The chromium nitrate solution was slowly added to the sodium 2-ethylhexanoate solution with good stirring. When the addition was complete, 500 ml of hexane were added and stirring was continued for 10 minutes. The layers were separated and the hexane layer containing the aquated chromium III tri-2-ethylhexanoate was washed with dilute sodium hydroxide solution, water, dilute sodium carbonate solution and finally with distilled water. The hexane solution was then dried over anhydrous magnesium sulfate. Most of the hexane was removed under reduced pressure and the resulting concentrate was slowly added to 500 ml of acetone. The resulting blue granular solid was filtered and air dried to yield 130 g (54%) of aquated chromium tri-2-ethylhexanoate. Molecular weight determination indicated that the compound is polymeric in nature, probably due to the oxygen bridging of chromium atoms.

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 385 mg (0.86 mmol) of benzhydryl (E)-(2S,3S,5R)-3-(2-chloro- vinyl) -3- methyl-4,4,7-trioxo-4-thia- 1-aza-bicyclo [3.2.0]heptane-2-carboxylate are dissolved in 2.3 ml of m-cresol under argon and stirred at 50° C. for 4 hours. Subsequently, the mixture was diluted with 15 ml of isobutyl methyl ketone, treated with 0.50 ml of sodium 2-ethylcaproate (2N solution in ethyl acetate) and extracted three times with 8 ml of water each time. The combined aqueous phases were washed once with 10 ml of isobutyl methyl ketone, lyophilized and the lyophilizate obtained was chromatographed over polymeric hydrophobic gel with water as the eluent. Yield: 57 mg (32%) MS: (M--Na)- 278.2 IR (KBr): 1780, 1626, 1564, 1417, 1329, 1145 cm-1 extracted three times with 8 ml of water each time The combined aqueous phases were washed once with 10 ml of isobutyl methyl ketone the lyophilizate obtained was chromatographed over polymeric hydrophobic gel with water as the eluent

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 385 mg (0.86 mmol) of benzhydryl (E)-(2S,3S,5R)-3-(2-chloro- vinyl) -3- methyl-4,4,7-trioxo-4-thia- 1-aza-bicyclo [3.2.0]heptane-2-carboxylate are dissolved in 2.3 ml of m-cresol under argon and stirred at 50° C. for 4 hours. Subsequently, the mixture was diluted with 15 ml of isobutyl methyl ketone, treated with 0.50 ml of sodium 2-ethylcaproate (2N solution in ethyl acetate) and extracted three times with 8 ml of water each time. The combined aqueous phases were washed once with 10 ml of isobutyl methyl ketone, lyophilized and the lyophilizate obtained was chromatographed over polymeric hydrophobic gel with water as the eluent. Yield: 57 mg (32%) MS: (M--Na)- 278.2 IR (KBr): 1780, 1626, 1564, 1417, 1329, 1145 cm-1 extracted three times with 8 ml of water each time The combined aqueous phases were washed once with 10 ml of isobutyl methyl ketone the lyophilizate obtained was chromatographed over polymeric hydrophobic gel with water as the eluent

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 95 mg (0.2 mmol) of benzhydryl (Z)-(2S,3S,5R)-3-(2-cyanoethenyl)- 3-methyl-4,4,7-trioxo-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylate were dissolved in 3 ml of m-cresol and stirred at 50° C. for 45 minutes. The reaction mixture was treated with 10 ml of isobutyl methyl ketone and 120 μl of sodium 2-ethylcaproate (2N in ethyl acetate, 1.1 eq.). The mixture was extracted twice with 3 ml of water each time, the combined aqueous phases are washed with 10 ml of isobutyl methyl ketone and lyophilized. The yellow lyophilizate was dissolved in 1.3 ml of water and chromatographed over polymeric hydrophobic gel. Yield: 50 mg (80%) of colorless lyophilizate IR (KBr): 2222, 1782, 1626, 1395, 1323, 1141 cm-1 1 H-NMR (250MHz, D2O): δ[ppm]=1.94(s,3H), 3.47(dd,1H,J=16Hz, 1.6Hz, 6-H), 3.73(dd, 1H, J=16Hz, 4.4Hz, 6-H), 4.80(s,1H,2-H), 5.19(dd, 1H, J=16Hz, 4.4Hz,5-H), 6.15(d.1H,J=12Hz,=CH), 6.68 (d,1 H,J=12Hz,=CH). The mixture was extracted twice with 3 ml of water each time the combined aqueous phases are washed with 10 ml of isobutyl methyl ketone The yellow lyophilizate was dissolved in 1.3 ml of water chromatographed over polymeric hydrophobic gel

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 95 mg (0.2 mmol) of benzhydryl (Z)-(2S,3S,5R)-3-(2-cyanoethenyl)- 3-methyl-4,4,7-trioxo-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylate were dissolved in 3 ml of m-cresol and stirred at 50° C. for 45 minutes. The reaction mixture was treated with 10 ml of isobutyl methyl ketone and 120 μl of sodium 2-ethylcaproate (2N in ethyl acetate, 1.1 eq.). The mixture was extracted twice with 3 ml of water each time, the combined aqueous phases are washed with 10 ml of isobutyl methyl ketone and lyophilized. The yellow lyophilizate was dissolved in 1.3 ml of water and chromatographed over polymeric hydrophobic gel. Yield: 50 mg (80%) of colorless lyophilizate IR (KBr): 2222, 1782, 1626, 1395, 1323, 1141 cm-1 1 H-NMR (250MHz, D2O): δ[ppm]=1.94(s,3H), 3.47(dd,1H,J=16Hz, 1.6Hz, 6-H), 3.73(dd, 1H, J=16Hz, 4.4Hz, 6-H), 4.80(s,1H,2-H), 5.19(dd, 1H, J=16Hz, 4.4Hz,5-H), 6.15(d.1H,J=12Hz,=CH), 6.68 (d,1 H,J=12Hz,=CH). The mixture was extracted twice with 3 ml of water each time the combined aqueous phases are washed with 10 ml of isobutyl methyl ketone The yellow lyophilizate was dissolved in 1.3 ml of water chromatographed over polymeric hydrophobic gel

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

Procedure: To a suspension of 2-mercapto-4-pyridinecarboxylic acid (7.65 g) in a mixture of tetrahydrofuran (60 ml) and methanol (60 ml) was added a solution of sodium 2-ethylhexanoate in isopropyl alcohol (27.5%) and the mixture was stirred for 2 days at room temperature. The reaction mixture was evaporated and the residue was washed with a mixture of acetone and ethanol. The crystals were collected by filtration dried over phosphorus pentoxide to give disodium 2-sulfido-4-pyridinecarboxylate (8.5 g). The reaction mixture was evaporated the residue was washed with a mixture of acetone and ethanol The crystals were collected by filtration dried over phosphorus pentoxide

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

Procedure: To a suspension of 2-mercapto-4-pyridinecarboxylic acid (7.65 g) in a mixture of tetrahydrofuran (60 ml) and methanol (60 ml) was added a solution of sodium 2-ethylhexanoate in isopropyl alcohol (27.5%) and the mixture was stirred for 2 days at room temperature. The reaction mixture was evaporated and the residue was washed with a mixture of acetone and ethanol. The crystals were collected by filtration dried over phosphorus pentoxide to give disodium 2-sulfido-4-pyridinecarboxylate (8.5 g). The reaction mixture was evaporated the residue was washed with a mixture of acetone and ethanol The crystals were collected by filtration dried over phosphorus pentoxide

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

Procedure: 2.03 g of sodium 2-ethylhexanoate was dissolved in a mixture of 12.5 ml of N,N-dimethylacetamide and 50 ml of methanol, 5.0 g of cefpodoxime (7-[2-(2-amino-4-thiazolyl)-(Z)-2-(methoxyimino)acetamido]-3-methoxymethyl -3-cephem-4-carboxylic acid) was added thereto, and the mixture was stirred at room temperature for 30 minutes. Then, methanol was removed under a reduced pressure and 50 ml of acetone was added thereto. The solution was stirred for 30 minutes and filtered. The filtered solid was washed with 50 ml of acetone and then with 30 ml of isopropyl ether, and vacuum-dried at room temperature to give 4.98 g of pale yellow cefpodoxime sodium salt (yield: 95%). was added Then, methanol was removed under a reduced pressure and 50 ml of acetone was added The solution was stirred for 30 minutes filtered The filtered solid was washed with 50 ml of acetone with 30 ml of isopropyl ether, and vacuum-dried at room temperature

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

Procedure: 2.03 g of sodium 2-ethylhexanoate was dissolved in a mixture of 12.5 ml of N,N-dimethylacetamide and 50 ml of methanol, 5.0 g of cefpodoxime (7-[2-(2-amino-4-thiazolyl)-(Z)-2-(methoxyimino)acetamido]-3-methoxymethyl -3-cephem-4-carboxylic acid) was added thereto, and the mixture was stirred at room temperature for 30 minutes. Then, methanol was removed under a reduced pressure and 50 ml of acetone was added thereto. The solution was stirred for 30 minutes and filtered. The filtered solid was washed with 50 ml of acetone and then with 30 ml of isopropyl ether, and vacuum-dried at room temperature to give 4.98 g of pale yellow cefpodoxime sodium salt (yield: 95%). was added Then, methanol was removed under a reduced pressure and 50 ml of acetone was added The solution was stirred for 30 minutes filtered The filtered solid was washed with 50 ml of acetone with 30 ml of isopropyl ether, and vacuum-dried at room temperature