Methanesulfonyl chloride → 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)-methoxyimino-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 (×3) 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 (9H, s) overlapping 1.4-1.7 (4H, m), 1.73-1.94 (2H, m), 3.38-3.58 (3H, m), 3.95-4.00 (1H, m), 4.07 (3H, s), 4.54-4.59 (1H, m), 5.02 (1H, d, J4.8 Hz), 5.90 (1H, dd, J4.5, 9.1 Hz) 6.74 (1H, s), 6.86 (1H, d, J8.8 Hz), 7.04 (1H, s) and 7.30 (15H, s). [Mass spectrum: +ve ion (3-nitrobenzyl alcohol, sodium acetate) MNa+ (788)].

Provenance & Evidence