Pyridine → (4-methoxyphenyl)methyl (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-8-oxo-3-[(2R)-oxolan-2-yl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

Participants

Reaction Conditions

Reaction Steps

Methanesulphonyl chloride (198 μl, 2.56 mmol) was added to 2-(2-aminothiazol-4-yl)-2-(Z)-methoxyiminoacetic acid (515 mg, 2.56 mmol) and N,N-diisopropylethylamine (447 μl, 2.57 mmol) in DMF (8 ml) at -30° C. After stirring at -30±10° C. for 30 min., a solution of 4-methoxybenzyl (6R,7R)-7-amino-3-[(R)-tetrahydrofuran-2-yl]ceph-3-em-4-carboxylate (915 mg, 2.35 mmol) in DMF (5 ml) was added, followed by pyridine (207 μl, 2.56 mmol). The reaction mixture was transferred to an ice-bath and stirring continued for a further 1.5 h. After dilution with ethyl acetate, the solution was washed successively with saturated sodium hydrogen carbonate solution, 5% aqueous citric acid, water (×2) and brine, dried and then concentrated in vacuo. The residue was triturated several times with diethyl ether to yield the title compound as an off-white solid (1.06 g, 79%); νmax (CH2Cl2) 3390, 1783, 1730, 1687, 1606, 1516 cm-1 ; δH (CDCl3, 250 MHz) 1.55-1.70 (1H, m), 1.86-1.98 (2H, m), 2.0-2.14 (1H, m), 3.40 and 3.59 (2H, ABq, J 17.8 Hz), 3.78-3.93 (2H, m), 3.91 (3H, s), 4.12 (3H, s), 5.04 (1H, d, J 4.7 Hz), 5.15 (1H, dd, J 7.7, 7.7 Hz), 5.21 (2H, s), 5.87 (1H, dd, J 8.7, 4.7 Hz), 6.55 (2H, br. s, exch.), 6.90 (2H, d, J 8.6 Hz), 7.05 (1H, s), 7.36 (2H, d, J 8.6 Hz), 7.65 (1H, br. d, J 8.7 Hz). [Mass spectrum: +ve ion (thioglycerol) MH+ (574)].

Provenance & Evidence