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

Participants

Reaction Conditions

Reaction Steps

Mesyl chloride (121 mg, 82 μl) was added to 2-(Z)-methoxy-imino-2-(2-tritylaminothiazol-4-yl)acetic acid hydrochloride (466 mg) and N,N-diisopropylethylamine (252 mg, 340 μl) in dry DMF (10 ml) at -50° C. under argon and stirred at -50° C. for 1 h. Then t-butyl (6R,7R)-7amino-3- (tetrahydropyran-2-yl)-ceph-3-em-4-carboxylate (Isomer A, 300 mg) in dry DMF (5 ml) followed by pyridine (70 mg, 72 μl) were added and reaction mixture left for a further 1 h whilst warming to ambient temperature. The reaction mixture was partitioned between ethyl acetate and water, reextracted with ethyl acetate, organic extracts washed with water (x3) and brine, dried, concentrated and flash chromatography (eluting with 30, 40, 50, 60% ethyl acetate in hexane) to afford the title compound as a pale yellow foam (420 mg, 62%); νmax (CH2Cl2) 3420, 1784, 1732 (shoulder), 1717, 1685 cm-1 ; δH (CDCl3), 1.53 (9 H, s) overlapping 1.4-1.7 (4 H, m), 1.73-1.94 (2 H, m), 3.38-3.58 (3 H, m), 3.95-4.00 (1 H, m), 4.07 (3 H, s), 4.54-4.59 (1 H, m), 5.02 (1 H, d, J4.8 Hz), 5.90 (1 H, dd, J4.5, 9.1 Hz) 6.74 (1 H, s), 6.86 (1 H, d, J8.8 Hz), 7.04 (1 H, s) and 7.30 (15 H, s). [Mass spectrum: +ve ion (3-nitrobenzyl alcohol, sodium acetate) MNa+ (788)].

Provenance & Evidence