反应详情

温度

-50 °C

Mesyl chloride (121mg, 82μl) was added to 2-(Z)-methoxyimino-2-(2-tritylaminothiazol-4-yl)acetic acid hydrochloride (466mg) and N,N-diisopropylethylamine (252mg, 340μl) in dry DMF (10ml) at -50° C. under argon and stirred at -50° C. for 1h. Then t-butyl (6R,7R)-7amino-3-(tetrahydropyran-2-yl)-ceph-3-em-4-carboxylate (Isomer A, 300mg) in dry DMF (5ml) followed by pyridine (70mg, 72μl) were added and reaction mixture left for a further 1h 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 (420mg, 62%); vmax (CH2Cl2) 3420, 1784, 1732 (shoulder), 1717, 1685cm-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, J4.8Hz), 5.90 (1H, dd, J4.5, 9.1Hz) 6.74 (1H, s), 6.86 (1H, d, J8.8Hz), 7.04 (1H, s) and 7.30 (15H, s). [Mass spectrum: +ve ion (3-nitrobenzyl alcohol, sodium acetate) MNa+ (788)].

1. additionwere added
2. customreaction mixture
3. temperaturewarming to ambient temperature
4. customThe reaction mixture was partitioned between ethyl acetate and water
5. washwashed with water (x3) and brine
6. customdried
7. concentrationconcentrated
8. washflash chromatography (eluting with 30,40,50,60% ethyl acetate in hexane)