反应详情

A solution of 3,4-dichlorophenylthioacetyl chloride (prepared by the action of oxalyl chloride (8.4 cc) on the corresponding acid (3.99 g) in ethyl ether (48 cc), and replacement of the solvent) in ethyl acetate (20 cc) is added, in 10 minutes, to a solution of 7-amino-2-benzhydryloxycarbonyl-3-(2-nicotinoylamino-thiazol-5-yl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene (6.43 g) in N,N-dimethylacetamide (25 cc) at 0° C. After 1 hour at 0° C. followed by 40 minutes at a temperature of between 0 ° and 20° C., the reaction mixture is poured into ethyl acetate (250 cc) and this mixture is washed with distilled water (3×100 cc) and then with a saturated sodium chloride solution (100 cc). The organic phase is dried and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C. The residue is filtered on a column of silica (0.02-0.5 mm) (40 g), elution being carried out with a mixture (2 liters) of methylene chloride and methanol (95:5 by volume). The residue obtained after concentrating to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C. is crystallised from methylene chloride (20 cc) to give 2-benzhydryloxycarbonyl-7-(3,4-dichlorophenylthio)-acetamido-3-(2-nicotinoylamino-thiazol-5-yl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene (2.9 g) in the form of a pale yellow crystalline solid.

1. washthis mixture is washed with distilled water (3×100 cc)
2. customThe organic phase is dried
3. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C
4. filtrationThe residue is filtered on a column of silica (0.02-0.5 mm) (40 g), elution
5. customThe residue obtained
6. concentrationafter concentrating to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C.
7. customis crystallised from methylene chloride (20 cc)