2,2,3-tribromopropanal

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of benzhydryl 7β-amino-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylate (2.473 g, 5.000 mmol) in methylene chloride (35 ml) was added under ice-cooling a solution of 2,2,3-tribromopropanal (1.474 g, 5.000 mmol) in methylene chloride (5 ml) and the mixture was stirred for 20 minutes. The reaction mixture was cooled to -20° C., N,N-dimethylaniline (3.5 ml) was added thereto and then thionyl chloride (0.5 ml, 6.9 mmol) was added dropwise. After stirring under ice-cooling for 2 hours, the reaction mixture was poured into a mixture of a saturated aqueous solution of potassium hydrogen sulfate (100 ml) with ice (100 g) followed by extraction with methylene chloride (400 ml, twice). The methylene chloride layer was washed successively with an ice-cooled saturated aqueous solution of potassium hydrogen sulfate (200 ml) and then ice-water (200 ml). Thereafter, the organic layer was dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and the residue was crystallized with the addition of ethyl acetate (20 ml). The crystalline substance was recovered by filtration, washed with a small volume of ice-cooled methylene chloride and dried under reduced pressure to yield 2.720 g (71%) of the title compound as a pale yellow crystal. This product gradually decomposed with coloration at 90° C. and higher. After stirring under ice- cooling for 2 hours followed by extraction with methylene chloride (400 ml The methylene chloride layer was washed successively with an ice- cooled saturated aqueous solution of potassium hydrogen sulfate (200 ml) Thereafter, the organic layer was dried over anhydrous magnesium sulfate The solvent was distilled off under reduced pressure the residue was crystallized with the addition of ethyl acetate (20 ml) The crystalline substance was recovered by filtration washed with a small volume of ice- cooled methylene chloride dried under reduced pressure

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of benzhydryl 7β-amino-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylate (2.473 g, 5.000 mmol) in methylene chloride (35 ml) was added under ice-cooling a solution of 2,2,3-tribromopropanal (1.474 g, 5.000 mmol) in methylene chloride (5 ml) and the mixture was stirred for 20 minutes. The reaction mixture was cooled to -20° C., N,N-dimethylaniline (3.5 ml) was added thereto and then thionyl chloride (0.5 ml, 6.9 mmol) was added dropwise. After stirring under ice-cooling for 2 hours, the reaction mixture was poured into a mixture of a saturated aqueous solution of potassium hydrogen sulfate (100 ml) with ice (100 g) followed by extraction with methylene chloride (400 ml, twice). The methylene chloride layer was washed successively with an ice-cooled saturated aqueous solution of potassium hydrogen sulfate (200 ml) and then ice-water (200 ml). Thereafter, the organic layer was dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and the residue was crystallized with the addition of ethyl acetate (20 ml). The crystalline substance was recovered by filtration, washed with a small volume of ice-cooled methylene chloride and dried under reduced pressure to yield 2.720 g (71%) of the title compound as a pale yellow crystal. This product gradually decomposed with coloration at 90° C. and higher. After stirring under ice- cooling for 2 hours followed by extraction with methylene chloride (400 ml The methylene chloride layer was washed successively with an ice- cooled saturated aqueous solution of potassium hydrogen sulfate (200 ml) Thereafter, the organic layer was dried over anhydrous magnesium sulfate The solvent was distilled off under reduced pressure the residue was crystallized with the addition of ethyl acetate (20 ml) The crystalline substance was recovered by filtration washed with a small volume of ice- cooled methylene chloride dried under reduced pressure

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Iodo-4-nitroaniline (5.3 g) in acetic acid (40 ml) was treated with 2,2,3 tribromopropanal (5.9 g) and the mixture was heated at 110° C. for 2 h after which it was cooled to room temperature and filtered. The filtered solid was washed with diethyl ether, suspended in water and treated with saturated sodium hydrogen carbonate. Extraction with ethyl acetate, drying over sodium sulphate, filtration and evaporation under reduced pressure gave the desired product, 3-bromo-8-iodo-6-nitro-quinoline, as a yellow solid after chromatography (silica; hexane/ethyl acetate) (M+379). was cooled to room temperature filtered The filtered solid was washed with diethyl ether treated with saturated sodium hydrogen carbonate Extraction with ethyl acetate drying over sodium sulphate, filtration and evaporation under reduced pressure

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of benzhydryl 7β-amino-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylate (2.473 g, 5.000 mmol) in methylene chloride (35 ml) was added under ice-cooling a solution of 2,2,3-tribromopropanal (1.474 g, 5.000 mmol) in methylene chloride (5 ml) and the mixture was stirred for 20 minutes. The reaction mixture was cooled to -20° C., N,N-dimethylaniline (3.5 ml) was added thereto and then thionyl chloride (0.5 ml, 6.9 mmol) was added dropwise. After stirring under ice-cooling for 2 hours, the reaction mixture was poured into a mixture of a saturated aqueous solution of potassium hydrogen sulfate (100 ml) with ice (100 g) followed by extraction with methylene chloride (400 ml, twice). The methylene chloride layer was washed successively with an ice-cooled saturated aqueous solution of potassium hydrogen sulfate (200 ml) and then ice-water (200 ml). Thereafter, the organic layer was dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and the residue was crystallized with the addition of ethyl acetate (20 ml). The crystalline substance was recovered by filtration, washed with a small volume of ice-cooled methylene chloride and dried under reduced pressure to yield 2.720 g (71%) of the title compound as a pale yellow crystal. This product gradually decomposed with coloration at 90° C. and higher. After stirring under ice- cooling for 2 hours followed by extraction with methylene chloride (400 ml The methylene chloride layer was washed successively with an ice- cooled saturated aqueous solution of potassium hydrogen sulfate (200 ml) Thereafter, the organic layer was dried over anhydrous magnesium sulfate The solvent was distilled off under reduced pressure the residue was crystallized with the addition of ethyl acetate (20 ml) The crystalline substance was recovered by filtration washed with a small volume of ice- cooled methylene chloride dried under reduced pressure