Methanol → Diphenylmethyl 7beta-Amino-3-(6-methyl-2-oxo-2H-pyran-4-ylthiomethyl)ceph-3-em-4-carboxylate

A stirred solution of diphenylmethyl 3-(6-methyl-2-oxo-2H-pyran-4-ylthiomethyl)-7β-phenylacetamidoceph-3-em-4-carboxylate (1.55 g) in dichloromethane (20 ml) was cooled to -15° to -20° C. and N-methylmorpholine (0.54 ml) was added followed by a solution of phosphorus pentachloride in dichloromethane (19 ml of a solution containing 40 mg ml-1). The mixture was maintained at the same temperature for 0.5 h and then methanol (4.9 ml) was added and the mixture stirred at room temperature for 0.5 h. Water (6.6 ml) was then added and the mixture was vigorously stirred for 0.5 h. Most of the dichloromethane was removed on a rotary evaporator and the residue was stirred with water and ethyl acetate. The pH of the aqueous phase was adjusted to 6.2 with 1N aqueous ammonia. The organic phase was separated, washed with water and brine, dried over magnesium sulphate and evaporated. The product (1.20 g) was isolated by column chromatography using gradient elution (Kieselgel 1:1 hexane:ethyl acetate going to neat ethyl acetate). υmax (CHCl3) 1785, 1710cm-1 δ(CDCl3) 1.79 (2H, S). 2.18 (3H, S) 3.42 (1H, d, J 18.2Hz), 3.61 (1H, d, J 18.3Hz), 3.80 (1H, d, J 12.2Hz), 3.90 (1H, d, J 12.2Hz), 4.80 (1H, d, J 5.2Hz), 4.96 (1H, d, J 5.1Hz), 5.66 (1H, d, J ca 1Hz), 5.78 (1H, d, J ca 1Hz), 7.00 (1H, s), 7.2-7.45 (10H, m). [Mass spectrum: +ve ion (3NOBA, Na+) MNa+ 543].

1. temperatureThe mixture was maintained at the same temperature for 0.5 h
2. stirringthe mixture was vigorously stirred for 0.5 h
3. customMost of the dichloromethane was removed on a rotary evaporator
4. stirringthe residue was stirred with water and ethyl acetate
5. customThe organic phase was separated
6. washwashed with water and brine
7. dry with materialdried over magnesium sulphate
8. customevaporated

ORD-Eintrag

ord-09a8e21c8dc94580b87ba1f83c384c33

Quelldatensatz

uspto-grants-1992_10

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US05158946