Reaction SMILES: ClC(Cl)C([O:5][N:6]=[C:7]([C:11]1[S:12][CH:13]=[CH:14][CH:15]=1)[C:8](Cl)=[O:9])=O.Cl.[NH2:18][C@@H:19]1[C:55](=[O:56])[N:21]2[C:22]([C:39]([O:41][CH:42]([C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=3)[C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=3)=[O:40])=[C:23]([CH2:26][S:27][C:28]3[O:29][C:30]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)=[N:31][N:32]=3)[CH2:24][S:25][C@H:20]12.C1OC1C>C(Cl)Cl>[OH:5][N:6]=[C:7]([C:11]1[S:12][CH:13]=[CH:14][CH:15]=1)[C:8]([NH:18][C@@H:19]1[C:55](=[O:56])[N:21]2[C:22]([C:39]([O:41][CH:42]([C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=3)[C:43]3[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=3)=[O:40])=[C:23]([CH2:26][S:27][C:28]3[O:29][C:30]([C:33]4[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=4)=[N:31][N:32]=3)[CH2:24][S:25][C@H:20]12)=[O:9]
Reactant: N[C@@H]1C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)=C(CSc3nnc(-c4ccccc4)o3)CS[C@H]12
Reactant: O=C(Cl)C(=NOC(=O)C(Cl)Cl)c1cccs1
Agent: CC1CO1
Agent: Cl
Solvent: ClCCl
Product: O=C(N[C@@H]1C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)=C(CSc3nnc(-c4ccccc4)o3)CS[C@H]12)C(=NO)c1cccs1
Reaction time: 0.5 h

Procedure:
A solution of 2-dichloroacetoxyimino-2-(thien-2-yl)-acetyl chloride (syn-isomer) in methylene dichloride (7 ml. of 15% solution; was added, over 5 minutes, to a stirred solution of diphenylmethyl 7β-amino-3-(5-phenyl-1,3,4-oxadiazol-2-ylthiomethyl)-ceph-3-em-4-carboxylate hydrochloride (1.779 g.) and propylene oxide (1.5 ml.) in dry methylene dichloride (25 ml.). After stirring for a further 30 minutes, the solution was washed with saturated aqueous sodium bicarbonate, water and brine (25 ml. of each), and dried and evaporated to a foam (2.34 g.). A solution of this foam in benzene (10 ml.) was purified by chromatography on kieselgel with benzene:ethyl acetate (10:1) as eluent. Appropriate fractions were combined and evaporated to dryness in vacuo, and the residue was triturated with ether (25 ml.) to give diphenylmethyl 7β-[2-hydroxyimino-2-(thien-2-yl)-acetamido]-3-(5-phenyl-1,3,4-oxadiazol-2-ylthiomethyl)-ceph-3-em-4-carboxylate as colourless prisms (870 mg., 41%). A suspension of this ester (810 mg) in a mixture of trifluoroacetic acid (3 ml.) and anisole (0.8 ml.) was shaken at 23° until all the solid had dissolved (ca. 10 minutes.). The reagents were evaporated at 40° (2 mm), and the residue was dissolved in ethyl acetate. The solution was extracted with aqueous sodium bicarbonate, the alkaline extract covered with ethyl acetate and acidified to pH 2 with 2N-hydrochloric acid. The organic phase was separated, and washed with water, and brine and the solvent evaporated in vacuo. The residue was dissolved in acetone, the solution treated with some charcoal and filtered through a pad of kieselguhr; the filtrate was dried and evaported to a foam (470 mg.). A solution of this foam in ethyl acetate was run into petroleum to give the title acid as a colourless, amorphous solid (410 mg., 66%), [α]D23 -118° (c 1.08, acetone), λmax. (pH 6 phosphate buffer) 274 nm (ε 28,800), νmax. (Nujol) 3280 (NH), 1786 (β-lactam), 1720 (CO2H), and 1672 and 1530 cm.-1 (CONH), τ (DMSO-d6) values include 0.24 (NH, doublet, J 8 Hz.), 4.15 (C-7 H, double doublet, J 4.5 and 8 Hz.), 4.78 (C-6 H, doublet, J 4.5 Hz.).