Dicyclohexylcarbodiimide → HCID 53709484, compound

Participants

Reaction Steps

N,N'-Dicyclohexylcarbodiimide (1.24 g) is added to a solution, cooled to +5° C., of 7-amino-2-benzhydry-loxycarbonyl-8-oxo-3-(2-nicotinoylaminothiazol-5-yl)-5-thia- 1-azabicyclo[4.2.0]oct-2-ene 5-oxide (2.8g), the syn isomer of 2-methoxyimino-2-(2-tritylaminothiazol-4-yl)-acetic acid (2.66 g) and 1-hydroxybenzotriazole (0.82 g) in N,N-dimethylformamide (20 cc), and the reaction mixture is then stirred for 1 hour at +5° C. and then for 64 hours at 20° C; after filtration, the reaction mixture is diluted with chloroform (200 cc) and washed with a 5% strength solution of sodium bicarbonate (100 cc), water (100 cc) and then a saturated solution of sodium chloride (100 cc). After drying over magnesium sulphate, the organic phase is concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C. to give the crude product (5 g). This crude product (10 g) is chromatographed on a column containing silica gel (0.2-0.06 mm) (250 cc), elution being carried out successively with a mixture of methylene chloride and ethyl acetate (75/25 by volume) (1 liter), then a mixture of methylene chloride and ethyl acetate (50/50 by volume) (1 liter) and then ethyl acetate (2 liters) and a mixture of ethyl acetate and methanol (80/20 by volume) (1 liter) and 100 cc fractions being collected. Fractions 19 to 33 are combined and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C. to give the syn isomer of 2-benzhydryLoxycarbonyl-7-[2-methoxyimino-2-(2-tritylaminothiazol-4-yl)-acetamido]-8-oxo-3-(2-nicotinoylaminothiazol-5-yl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene 5-oxide (6.2 g) in the form of an orange solid.

Provenance & Evidence