Dicyclohexylcarbodiimide → 8-Oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene

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Reaction Steps

1-Hydroxybenzothiazole (3.24 g) and N,N'-dicyclohexylcarbodiimide (4.95 g) are added to a solution, cooled to 5° C., of 7-amino-2-benzhydryloxycarbonyl-3-[2-(pyridin-3-yl-amino)-thiazol-5-yl]-8-oxo-5-thia-1-azabicyclo-[4.2.0]oct-2-ene (10.83 g) and the syn isomer of 2-methoxyimino-2-(2-tritylaminothiazol-4-yl)-acetic acid (10.65 g) in dry N,N-dimethylformamide (200 cc). The mixture is stirred for 30 minutes at +5° C. and then for 4 hours at 20° C. Acetic acid (1 cc) is added to the reaction mixture and the precipitate is then filtered off. The filtrate is diluted with ethyl acetate (900 cc) and the organic phase is washed successively with distilled water (2×500 cc), a decinormal solution of hydrochloric acid (500 cc), a semi-saturated solution of sodium bicarbonate (500 cc), distilled water (2×500 cc) and a semi-saturated solution of sodium chloride (500 cc). After the organic phase has been dried over magnesium sulphate and filtered and the filtrate concentrated under reduced pressure (30 mm Hg; 4 kPa), a hard yellow foam is obtained which is purified by chromatography on a column (height 61 cm, diameter 4.8 cm) containing silica gel (0.06-0.20 mm), elution being carried out with a 25/75 (by volume) mixture of cyclohexane and ethyl acetate (2 liters) and ethyl acetate (500 cc) and 250 cc fractions being collected. Fractions 5 to 14 are combined and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C. This gives the syn isomer of 2-benzhydryloxycarbonyl-7-[2-methoxyimino-2-(2-tritylaminothiazol-4-yl)-acetamido]-3-[2-pyridin-3-yl-amino)-thiazol-5-yl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene (14.6 g) in the form of a hard, bright yellow foam.

Provenance & Evidence