Methanesulfonyl chloride → HCID 20402445, compound

Participants

Reaction Conditions

Reaction Steps

Thionicotinamide (28.2 g) and pyridine (16.5 cc) are added to a solution of 2-benzhydryloxycarbonyl-3-(1-bromo-2-oxoethyl)-7-t-butoxycarbonylamino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene (mixture of the diastereoisomers) (120 g) in tetrahydrofuran (1,200 cc). The reaction mixture is stirred at 50° C. for 80 minutes. After cooling to +5° C., methanesulphonyl chloride (15.8 cc) and triethylamine (57.3 cc) are added successively in the course of 5 minutes. The reaction mixture is kept for 30 minutes at +5° C. and then reheated to 20° C. and poured into a mixture of ethyl acetate (1 liter) and a 5% strength solution of sodium bicarbonate (2 liters). The organic phase is washed with a 5% strength solution of sodium bicarbonate (2 liters) and then with a semi-saturated solution of sodium chloride (2 liters). After drying over magnesium sulphate and evaporation of the solvent to dryness under reduced pressure (4 kPa) at 30° C., the residue obtained is chromatographed on a column of diameter 9 cm containing silica gel (0.06-0.2 mm) (3.4 liters), 1 liter. fractions being collected. Elution is carried out successively with: methylene chloride (11 liters) and then the following mixtures (proportions by volume) of methylene chloride and ethyl acetate: 94/6 (16 liters), 88/12 (4 liters), 75/25 (12 liters) and 70/30 (10 liters). Fractions 32 to 52 are combined and concentrated to dryness and the residue is solidified with isopropyl ether to give 2-benzhydryloxycarbonyl-7-t-butoxycarbonylamino-8-oxo-3-[2-(pyridin-3-yl)-thiazol-5-yl]-5-thia-1-azabicyclo[4.2.0]-oct-2-ene (37.1 g) in the form of a beige solid.

Provenance & Evidence