Methanesulfonyl chloride → benzhydryl (6R,7R)-7-[[(2Z)-2-methoxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-3-[(2-methyl-6-oxopyran-4-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

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Reaction Steps

A stirred solution of 2-(2-tritylaminothiazol-4-yl)-2-(Z)-methoxyiminoacetic acid hydrochloride (470 mg) and N,N-diisopropylethylamine (0.34 ml) in dimethylformamide (4 ml) was cooled to -55° to -60° C. and methanesulphonyl chloride (0.075 ml) was added. The mixture was stirred at the same temperature for 0.5 h and then a solution of diphenymethyl 7β-amino-3-(6-methyl-2-oxo-2H-pyran-4-ylthiomethyl)ceph-3-em-4-carboxylate (450 mg) in dimethylformamide (4 ml) was added, followed by pyridine (0.071 ml). The mixture was stirred at 0° C. for 1.5 h and then partitioned between ethyl acetate and citric acid solution. The organic phase was then washed successively with water, sodium bicarbonate solution, water and brine. The solution was dried over magnesium sulphate and evaporated. The product (576 mg) was isolated by column chromatography of the residue using gradient elution (Kieselgel 1:1 hexane:ethyl acetate going to neat ethyl acetate). υmax (CHCl3) 3400, 1780, 1710 and 1680(s). δ(CDCl3) 2.18 (3H, s), 3.46 (1H, d, J 18.3Hz), 3.61 (1H, d, J 18.4Hz), 3.85 (1H, d, J 12.3Hz), 3.96 (1H, d, J 12.3Hz), 4.08 (3H, s), 5.08 (1H, d, J 4.9Hz), 5.69 (1H, s), 5.78 (1H, s), 5.96 (1H, dd, J 4.9 and 8.9Hz), 6.74 (1H, s), 6.81 (1H, d, J 8.8Hz), 6.97 (1H, s), 7.02 (1H, s), 7.2-7.5 (25H, m). [Mass spectrum: +ve ion (3NOBA, Na+) MNa+ 1196].

Provenance & Evidence