Propargyl bromide → benzhydryl 7-(2-phenylacetamido)-3-[2-(2-propynyl)-2H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylate-1-oxide

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Reaction Steps

A mixture of benzhydryl 7-(2-phenylacetamido)-3-(1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylate-1-oxide (78.0 g) in N,N-dimethylformamide (780 ml) was stirred to give a homogeneous solution and thereto were added 2-propynyl bromide (30.2 g) and triethylamine (38.5 g). The resulting solution was stirred for 22.3 hours at room temperature. The reaction mixture was added to ice-water (1.5 l) and the mixture was extracted with ethyl acetate (x 2). The extract was washed with water (x 4), dried over magnesium sulfate, treated with activated charcoal and then evaporated. The residue was pulverized in isopropyl ether, collected by filtration, washed with isopropyl ether and then dried. The obtained product (60.61 g) was subjected to column chromatography on silica gel (1.5 kg), using benzene and ethyl acetate (2:1) as an eluent. Fractions containing 2-(2-propynyl)-2H-tetrazolyl isomer, which were firstly eluted, were collected and then evaporated. The residue was pulverized in a mixture of isopropyl ether and n-hexane to give benzhydryl 7-(2-phenylacetamido)-3-[2-(2-propynyl)-2H-tetrazol-5-yl]thiomethyl-3-cephem-4-carboxylate-1-oxide (16.34 g).

Provenance & Evidence