Propylene Oxide → t-Butyl 3-acetoxymethyl-7beta-(pyrid-4-ylacetamido)ceph-3-em-4-carboxylate

Participants

Reaction Steps

A suspension of pyrid-4-ylacetyl chloride hydrochloride (6.0 g.) in ethyl acetate (50 ml) containing propylene oxide (12 ml.) was stirred, cooled in ice and treated dropwise with a solution of t-butyl 3-acetoxymethyl-7β-aminoceph-3-em-4-carboxylate (5.0 g.) in ethyl acetate (50 ml.). The mixture was stirred at 20° for 20 hours and then washed with saturated sodium bicarbonate solution and extracted with 2 N hydrochloric acid. The aqueous extract was washed with ethyl acetate, neutralised with saturated sodium bicarbonate solution and extracted with ethyl acetate. The extract was washed with water, dried over magnesium sulphate and evaporated to small bulk whereupon crystallisation began. The crystalline solid was washed well with petroleum spirit (bp. 40°-60°) and dried to give the title ester as a buff coloured powder (5.4 g., 80% based on amine). A portion (250 mg.) was recrystallised from ethyl acetate as white needles (170 mg.), [α]D +94° (c 0.9, DMSO) λmax. (EtOH) 256.5 nm (ε 9,900), νmax. (CHBr3) 3412 (NH), 1784 (β-lactam), 1736 (OAc), 1722 (CO2R), 1690 and 1512 cm.-1 (CONH), τ (d6 -DMSO) 0.81 (d, J 8 Hz; NH), 1.47 and 2.68 (2d, J 5 Hz; aromatic protons), 4.27 (q, J 8 and 5 Hz; C-7H), 4.85 (d, J 5 Hz; C-6 H), 5.01 and 5.36 (2d, J 13 Hz; C-3CH2), 6.38 (s; CH2CONH), 6.39 (s; C-2H2), 7.96 (s; OCOCH3), and 8.50 (s; C(CH3)3).

Provenance & Evidence