Methanesulfonyl chloride → (4-methoxyphenyl)methyl (6S,7S)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-8-oxo-3-(oxolan-2-yl)-4-oxa-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

Participants

Reaction Steps

A stirred mixture of 2-(Z)-methoxyimino-2-(2-aminothiazol-4-yl)acetic acid (III) (54 mg) and N,N-diisopropylethylamine (0.047 ml) in dimethylformamide (0.3 ml) was cooled to -55° to -60° C. and methanesulphonyl chloride (0.021 ml) was added. The mixture was stirred at the same temperature for 0.5 h and then a solution of 4-methoxybenzyl (6S,7S)-7-amino-8-oxo-3-(tetrahydrofuran-2-yl)-1-aza-4-oxabicyclo[4.2.0]oct-2-ene-2-carboxylate (II) (91 mg) in dimethylformamide (1 ml) was added, followed by p-ndine (0.022 ml). The mixture was then stirred at 0° C. for 1 h and then at room temperature for 0.5 h. The mixture was partitioned between ethyl acetate and aqueous citric acid solution and the organic phase was washed twice with water, then brine, dried over magnesium sulphate and evaporated. Column chromatography (silica gel, ethyl acetate as eluent) gave the title compound (88 mg. νmax (CHCl3) 1769, 1709, 1679 and 1613 cm-1 ; δ(CDCl3) 1.72-2.12 (4H, m), 3.35 (3H, s), 3.68-3.96 (4H, m), 3.76 (3H, s), 4.64 (1H, dd, J 9.19 and 15.89 Hz), 5.13 (3H, s), 5.20 (1H, t, J 6.77 Hz), 5.72 (1H, dd, J 4.14 and 8.91 Hz), 6.80 (1H, s), 6.93 (2H, d, J 8.68 Hz), 7.24 (2H, s), 7.37 (2H, d, J 8.66 Hz), 9.23 (1H, d, J 9 Hz).

Provenance & Evidence