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 Steps

Mesyl chloride (141μl, 1.8mmol) was added to 2-(Z)-methoxyimino-2-(2-tritylaminothiazol-4-yl)acetic acid hydrochloride (0.744g, 1.65mmol) and N,N-diisopropylethylamine (576μl, 3.3mmol) in DMF (5ml) at -40° C. The reaction mixture was stirred 0.5h at -30±10° C. then t-butyl (6R,7R)-7-amino-3-(tetrahydrofuran-2-yl)ceph-3-em-4-carboxylate, more mobile diastereoisomer (0.431g, 1.3mmol) in DMF (5ml) followed by pyridine (1471μl, 1.8mmol) were added. Stirred 1h 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 (0.83g, 84%); vmax (CH2Cl2) 3396, 3277, 1782, 1732, 1683, 1526, 1248, 1156 and 1051cm-1 ; δH [(CD3)2SO, 250MHz]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, J18.3Hz), 3.65-3.95 (2H, m), 3.81 (3H, s), 4.6-4.7 (1H, m), 5.14 (1H, d, J4.8Hz), 5.66 (1H, dd, J4.8, 7.9Hz), 6.70 (1H, s), 7.2-7.4 (15H, m), 8.88 (1H, s) and 9.54 (1H, d, J7.9Hz). [Mass spectrum: +ve ion (3-nitrobenzyl alcohol, sodium acetate) MNa+ (774)].

Provenance & Evidence