2288
Cummings et al.:
hydryl 7α-methoxy-3-azidomethyl-3-cephem-4-carboxylate-1,1-dioxide (370 mg, 33%). 1H NMR
spectrum: 3.56 s, 3 H (OCH3); 3.71 and 3.99 q, 2 H, J = 18.0 (H-2); 4.02 and 4.18 q, 2 H, J = 14.0
(CH2N3); 4.70 d, 1 H, J (6,7) = 1.5 (H-6); 5.19 d, 1 H, J (6,7) = 1.5 (H-7); 6.97 s, 1 H (CHPh2);
7.31 – 7.46 m, 10 H (arom.).
A solution of benzhydryl 7α-methoxy-3-azidomethyl-3-cephem-4-carboxylate-1,1-dioxide (3.1 g,
6.62 mmol) in ethylene glycol dimethyl ether (60 ml) was transferred to a steel bomb and cooled to
−78 °C; the reaction vessel was flushed with nitrogen for 15 min; 14.0 g of acetylene was taken in
the steel bomb and the reaction mixture was heated at 90 °C overnight. The steel bomb was cooled
in an ice-bath and the excess acetylene was slowly allowed to evaporate at room temperature. The
solvent was removed under reduced pressure. The crude product was purified over a silica gel col-
umn (elution with hexane–ethyl acetate, 1 : 1) to give a foam (1.9 g, 58%). Ether was added to the
1
foam and the precipitated solid was collected by filtration. H NMR spectrum: 3.55 s, 3 H (OCH3);
3.65 and 3.97 q, 2 H, J = 18.0 (H-2); 4.74 s, 1 H, (H-6); 5.16 s, 3 H (CH2-triazole + H-7); 7.10 s, 1 H
(CHPh2); 7.30 – 7.43 m, 10 H (arom.); 7.51 s, 1 H, and 7.67 s, 1 H (triazole).
Benzhydryl 7α-Methoxy-2-exo-methylene-3-[(1,2,3-triazolyl)methyl]-3-cephem-4-carboxylate-
1,1-dioxide7 (VIIIb)
To a solution of benzhydryl 7α-methoxy-3-[(1,2,3-triazolyl)methyl]-3-cephem-4-carboxylate-1,1-di-
oxide (VIb, 1.8 g, 3.85 mmol) in methylene chloride (30 ml) and 2-methyl-2-propanol (70 ml) was
added dimethylammonium chloride (940 mg, 11.54 mmol) and formaldehyde solution (37%, 410 mg,
13.5 mmol). The mixture was heated at 80 °C for 1.5 h and the solvent was removed. The residue
was taken in methylene chloride, washed with water, brine, dried (Na2SO4) and concentrated. The
residue was purified over a silica gel column (elution with hexane–ethyl acetate, 1 : 2) to give pure
benzhydryl 7α-methoxy-2-exo-methylene-3-[(1,2,3-triazolyl)methyl]-3-cephem-4-carboxylate-1,1-di-
oxide (VIIIb, 910 mg, 49%). 1H NMR spectrum: 3.57 s, 3 H (OCH3); 4.87 d, 1 H, J (6,7) = 2.0
(H-6); 5.01 and 5.47 q, 2 H, J = 15.0 (CH2-triazole); 5.29 d, 1 H, J (6,7) = 2.0 (H-7); 6.55 d, 1 H,
J = 2.6 (=CH2); 6.64 d, 1 H, J = 2.6 (=CH2); 7.06 s, 1 H (CHPh2); 7.30 – 7.37 m, 10 H (arom.); 7.51 s,
1 H, and 7.58 s, 1 H (triazole). Benzhydryl 7α-methoxy-2α-(1,1-dimethylethoxy)methyl-3-methyl-3-
cephem-4-carboxylate-1,1-dioxide (Vb) was isolated as a minor component (12%) from this experi-
1
ment. For H NMR spectrum see Table I.
p-Methoxybenzyl 7α-Methoxy-3-[(1,2,3-triazolyl)methyl]-3-cephem-4-carboxylate-1,1-dioxide7 (VIc)
A solution of p-methoxybenzyl-7β-amino-3-[(1,2,3-triazolyl)methyl]-3-cephem-4-carboxylate-1,1-di-
oxide7 (800 mg, 1.85 mmol) in dry ethyl acetate was cooled to 10 °C under nitrogen. Isopropyl nitrite
(0.247 g, 2.8 mmol) was added to the above solution followed by 3 drops of trifluoroacetic acid. The
reaction mixture was further stirred at 10 °C for 1 h and cooled to −5 °C. Rhodium octanoate dimer
(18 mg) was dissolved in a mixture of ethyl acetate (10 ml) and anhydrous methanol (2 ml) and the
mixture was stirred under nitrogen at 0 °C. After stirring for 30 min, 5 drops of triethylamine was
added (the color changes from light green to purple) and the solution was further cooled to −5 °C.
The above two solutions were mixed together at −5 °C and stirred for 2 h. The reaction mixture
was diluted with 50 ml of ethyl acetate, made acidic with glacial acetic acid, washed successively
with cold water, brine, dried (Na2SO4) and concentrated to give a dark brown foam which was puri-
fied on a silica gel column (elution with hexane–ethyl acetate, 1 : 1) to give pure p-methoxybenzyl-
7α-methoxy-3-[(1,2,3-triazolyl)methyl]-3-cephem-4-carboxylate-1,1-dioxide (VIc, 140 mg, 20%).
1H NMR spectrum: 3.54 s, 3 H (OCH3); 3.65 and 3.93 q, 2 H, J = 18.0 (H-2); 3.82 s, 3 H (OCH3);
4.70 d, 1 H, J (6,7) = 1.1 (H-6); 5.08 – 5.40 m, 5 H (CH2-triazole + CH2-benzylic + H-7); 6.91 d, 2 H
(arom.); 7.37 d, 2 H (arom.); 7.73 s, 2 H (triazole).
Collect. Czech. Chem. Commun. (Vol. 59) (1994)