Methanesulfonic Acid → 2-Benzhydryloxycarbonyl-3-(2-methoxycarbonylaminothiazol-5-yl)-8-oxo-7-(thien-2-yl-acetamido)-5-thia-1-azabicyclo[4.2.0]oct-2-ene

Participants

Reaction Conditions

Reaction Steps

Methanesulphonic acid (6 cc) is added to a solution of 2-benzhydryloxycarbonyl-7-t-butoxycarbonylamino-3-(2-methoxycarbonylamino-thiazol-5-yl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene (6.2 g) in acetonitrile (60 cc). After 15 minutes at 20° C., the reaction mixture is diluted with methylene chloride (150 cc) and with a half-saturated sodium bicarbonate solution (200 cc). The aqueous layer is washed with methylene chloride (3×50 cc) and the combined organic phases are washed with distilled water (2×100 cc), dried over magnesium sulphate and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C. Crude 7-amino-2-benzhydryloxycarbonyl-3-(2-methoxycarbonylamino-thiazol-5-yl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene (5.2 g) is obtained and is redissolved in dry tetrahydrofuran (50 cc). The solution obtained is cooled to 4° C. and treated with a solution of (thien-2-yl)-acetyl chloride (1.23 cc) in dry tetrahydrofuran (10 cc) and then with a solution of triethylamine (1.4 cc) in dry tetrahydrofuran (5 cc), in accordance with the working method described in Example 1. The crude product is chromatographed on a column (height: 32 cm, diameter: 6 cm) of silica gel (0.04-0.06 mm), elution being carried out under a pressure of 0.4 bar (40 kPa) with a 45.55 (by volume) mixture of cyclohexane and ethyl acetate, and 100 cc fractions being collected. Fractions 8 to 21, containing the pure product, are combined and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C. 2-Benzhydryloxycarbonyl-3-(2-methoxycarbonylamino-thiazol-5-yl)-8-oxo-7-(thien-2-yl-acetamido)-5-thia-1-azabicyclo[4.2.0]-oct-2-ene (1.91 g) is obtained in the form of a whitish solid.

Provenance & Evidence