Hydrochloric Acid → 3-Acetonyl-2-benzhydryloxycarbonyl-7-[2-methoxyimino-2-(2-tritylaminothiazol-4-yl)-acetamido]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene

Participants

Reaction Conditions

Reaction Steps

A 2.5M solution of phosgene in benzene (6.47 cc) is added, in the course of 20 minutes, to a suspension of 2-methoxyimino-2-(2-tritylaminothiazol-4-yl)-acetic acid (syn isomer) (5.84 g) in a mixture of methylene chloride (50 cc) and N,N-dimethylacetamide (1.23 cc) at -10° C. The reaction is left to proceed for 16 hours at -10° C. and a solution of 3-acetonyl-7-amino-2-benzhydryloxycarbonyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene (5.57 g) in a mixture of methylene chloride (50 cc) and triethylamine (5.6 cc) is then added in the course of 20 minutes. The mixture is stirred for 2 hours at -10° C. 0.5N hydrochloric acid (100 cc) is added and the organic phase is separated off by decantation. It is dried over sodium sulphate and concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 20° C. The residue is chromatographed on a column of Merck silica gel (0.06-0.2) (130 g) (diameter of the column: 3 cm; height: 37 cm). Elution is carried out with a 40/60 (by volume) ethyl acetate/cyclohexane mixture (2 liters), 100 cc fractions being collected. Fractions 8 to 14 are concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 20° C. This yields the syn isomer of 3-acetonyl-2-benzhydryloxycarbonyl-7-[2-methoxyimino-2-(2-tritylaminothiazol-4-yl)-acetamido]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene (4 g), which is identical to the product prepared above under A.

Provenance & Evidence