Pyridine → tert-butyl (6R,7R)-7-[[(2Z)-2-methoxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-8-oxo-3-(oxolan-2-yl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

Participants

Reaction Conditions

Reaction Steps

Mesyl chloride (14 μl, 1.8 mmol) was added to 2-(Z)-methoxyimino-2-(2-tritylaminothiazol-4-yl) acetic acid hydrochloride (0.744 g, 1.65 mmol) and N,N-diisopropylethylamine (576 μl, 3.3 mmol) in DMF (5 ml) at -40° C. The reaction mixture was stirred 0.5 h at -30±10° C. then t-butyl (6R,7R)-7-amino-3-(tetrahydrofuran-2-yl)ceph-3-em-4-carboxylate, more mobile diastereoisomer (0.431 g, 1.3 mmol) in DMF (5 ml) followed by pyridine (147 μl, 1.8 mmol) were added. Stirred 1 h without further cooling then diluted with ethyl acetate, washed twice with water and with brine, dried, concentrated and flash chromatographed on silica gel eluting with 30,35 and 40% ethyl acetate in hexane to give the title compound as a foam (0.83 g, 84%); νmax (CH2Cl2) 3396, 3277, 1782, 1732, 1683, 1526, 1248, 1156 and 1051 cm-1 ; δH [(CD3)2SO, 250 MHz] 1.47 (9H, s), 1.55-1.75 (1H, m), 1.8-2.0 (2H, m), 2.05-2.2 (1H, m), 3.44 and 3.50 (2H, ABq, J18.3 Hz), 3.65-3.95 (2H, m), 3.81 (3H, s), 4.6-4.7 (1H, m), 5.14 (1H, d, J4.8 Hz), 5.66 (1H, dd, J4.8, 7.9 Hz), 6.70 (1H, s), 7.2-7.4 (15H, m), 8.88 (1H, s) and 9.54 (1H, d, J7.9 Hz). [Mass spectrum: +ve ion (3-nitrobenzyl alcohol, sodium acetate) MNa+ (774)].

Provenance & Evidence