Dichloromethane → HCID 54407251, compound

Participants

Reaction Steps

Following the procedure described in Example 11B, a solution of the syn isomer of 2-benzhydryloxycarbonyl-7-[2-methoxyimino-2-(2-tritylaminothiazol-4-yl)-acetamido]-8-oxo-3-(2-oxoethyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene (product 13c) (2.3 g) in methylene chloride (15 cc), cooled to -40° C., is treated with a 0.5 M solution (5.5 cc), in methylene chloride, of the addition compound of chlorine and triphenyl phosphite. The reaction mixture is stirred for 3 hours at a temperature between -40° C. and -20° C. and then diluted with ethyl acetate (200 cc). The organic solution is decanted and washed with a semisaturated solution of sodium bicarbonate and sodium chloride (50 cc) and then a saturated solution of sodium chloride (3×50 cc). The aqueous phases are reextracted with ethyl acetate (50 cc) and the combined organic solutions are concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C. The residue is stirred with isopropyl ether (150 cc) for 16 hours. The precipitate is filtered off, washed with isopropyl ether (50 cc) and then redissolved in methylene chloride (50 cc) and fixed to silica gel (0.2-0.06) (8 g), which is deposited on a column of silica gel (0.06-0.04) (diameter of the column: 1.8 cm; height: 35 cm). Elution is carried out with a mixture of cyclohexane and ethyl acetate (75/25 by volume) under a pressure of 80 kPa, 50 cc fractions being collected. Fractions 5 to 7, containing the pure product, are combined and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C. This yields the syn isomer of 2-benzhydryloxycarbonyl-3-(2,2-dichloroethyl)-7-[2-methoxyimino-2-(2-tritylaminothiazol-4-yl)-acetamido]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene (product 13d) (0.25 g) in the form of a whitish solid.

Provenance & Evidence