Penam → (2R,3S,5R,6R) 2-(N-acetyl)carbamoyloxymethyl-2-methyl-6-phenoxyacetamidopenam-3-carboxylic acid p-nitrobenzyl ester

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Reaction Steps

A solution of (1S,3S,5R,6R) 2,2-dimethyl-6-phenoxyacetamidopenam-3-carboxylic acid-1-oxide p-nitrobenzyl ester (25.18 g, 50.0 mmol), acetyl isocyanate (8.50 ml, 9.53 g, 112 mmol), and dioxane (250 ml) was refluxed under nitrogen for 5 hours, cooled and concentrated in vacuo to a yellow foam. The foam was chromatographed on silica gel (1.7 Kg) with methylene chloride:acetone; 9:1; v:v to give four products; the 3-methyl-Δ3 -cephem; starting sulfoxide, the title penam, and the cephem (in order of elution). The penam fractions were concentrated to a colorless foam in 40.2% yield (11.80 g). Re-chromatography of a portion gave an analytical sample: m.p. 83°-85°; nmr 100 MHz (CDCl3) ppm 8.40 (1,s, ##STR59## 8.20 (2, d, J=8.5, 1/2 aromatic AB pNB), 7.56 (3, d, J=8.5 over m, 1/2 AB, pNB and C6 --NH), 7.5 (2, m) and 6.9 (3, m, O--Ph--H's), 5.7 (2, m's, C5 --C6 --H's), 5.32 (2, br s, pNB methylene), 4.88 (1, s, C3 --H), 4.56 (2, s, ##STR60## 4.26 and 4.06 (2, d's,J=11.5, AB of C2 --CH2O), 2.22 (3, s, ##STR61## and 1.47 (3, s, C2 --CH3); nmr 13C 4 carbonyls ca 170 ppm, carbamate carbonyl C 157.0, C2 singlet at 67.4, while C2 --CH2O is t at 72.3, and C2 --CH3 is q at 21.7.

Provenance & Evidence