反应详情

温度

-30 °C

Methanesulphonyl chloride (203 μl, 2.62 mmol) was added to 2-(2-aminothiazol-4-yl)-2-(Z)-methoxyiminoacetic acid (528 mg, 2.63 mmol) and N,N-diisopropylethylamine (458 μl, 2.63 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-[(S)-tetrahydrofuran-2-yl]ceph-3-em-4-carboxylate (930 mg, 2.38 mmol) in DMF (5 ml) was added, followed by pyridine (213 μl, 2.63 mmol). The reaction mixture was transferred to an ice-bath and stirring continued for a further 1 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 purified by chromatography on silica gel eluting with 50, 70 and 90% ethyl acetate in hexane to give the title compound as a yellow foam (1.138 g, 83%); νmax (CH2Cl2) 3389, 1783, 1732, 1682, 1516 cm-1 ; δH (CDCl3, 250 MHz) 1.53-1.70 (1H, m), 1.88-2.01 (2H, m), 2.28-2.41 (1H, m), 3.33 and 3.62 (2H, ABq, J 18.7 Hz), 3.79-3.98 (2H, m), 3.81 (3H, s), 4.08 (3H, s), 4.94 (1H, dd, J 9.0, 6.7 Hz), 5.04 (1H, d, J 4.8 Hz), 5.18 (2H, s), 5.88 (2H, br s, exch.), 5.98 (1H, dd, J 9.0, 4.8 Hz), 6.90 (2H, d, J 8.6 Hz), 6.94 (1H, s), 7.35 (2H, d, J 8.6 Hz), 7.50 (1H, br. d, J 9.0 Hz, exch.). [Mass spectrum: +ve ion (thioglycerol) MH+ (574)].

1. customThe reaction mixture was transferred to an ice-bath
2. stirringstirring
3. waitcontinued for a further 1 h
4. washAfter dilution with ethyl acetate, the solution was washed successively with saturated sodium hydrogen carbonate solution, 5% aqueous citric acid, water (×2) and brine
5. customdried
6. concentrationconcentrated in vacuo
7. customThe residue was purified by chromatography on silica gel eluting with 50, 70 and 90% ethyl acetate in hexane