反应详情

Phenylacetyl chloride (0.58 ml, 1.1 equiv.) was added to a stirred solution of t-butyl 7β-amino-3-methylceph-3-em-4-carboxylate (1.08 g, 4 mmole) in dimethylacetamide (2.5 ml) and acetonitrile (10 ml.) The mixture was stirred at ca. 25° for 45 minutes and the acetonitrile was removed in vacuo. Water (50 ml) and ethyl acetate (150 ml) were added and the organic phase was washed with water, 3% sodium hydrogen carbonate solution and water (50 ml of each), dried and evaporated. The residual colourless oil was dissolved in methylene chloride (10 ml) and cooled in an ice-bath while peracetic acid (40% w/v; 1.16 ml, 1.1 equiv.) was added dropwise. The solution was stirred at ca. 20° for 30 minutes and saturated sodium hydrogen carbonate solution (20 ml) was added. The organic phase was washed with water (50 ml), dried and evaporated to a white gelatinous solid, t.l.c. (acetone-methylene chloride; 1:4) Rf 0.49, 0.80, which was purified by chromatography on Kieselgel G (50g). Elution with acetonemethylene chloride (1:9) gave a pale yellow solid which was crystallised from acetone-light petroleum, b.p. 40°-60° (1:1; 10 ml) to give t-butyl 3-methyl-7β-phenylacetamidoceph-3-em-4-carboxylate, 1,1-dioxide (0.17 g, 11 %), m.p. 87 to 88°, [α]D + 36.5°, λmax. 259 nm (ε 8,150), νmax. (CHBr3) 3410 (NH), 1798 (acetidin-2-one), 1714 (CO2R) and 1680 and 1510 cm-1 (CONH), τ (CDCl3) 2.66 (5H,s; C6H5), 3.06 (1H,d, J 10.5 Hz; NH), 3.90 (1H,dd, J 10.5, 5Hz; C7 -H), 5.19 (1H,d, J 5 Hz; C6 -H), 6.09, 6.55 (2H, AB-q, J 18 Hz; C2 -H2), 6.34 (2H,s; C6H5CH2), 7.94 (3H,s; C3 -CH3), 8.49 (9H,s; CO2C(CH3)3). (Found: C, 56.9; 56.6; H, 5.8; 5.7; N, 6.3, 6.3; S, 7.4 C20H24N2O6S (420.5) requires C, 57.1; H, 5.75; N, 6.7; S, 7.6%). Further elution with acetone-methylene chloride (1:9) gave a white gelatinous solid which dissolved in acetone (10 ml) and reprecipitated by addition of light petroleum (b.p. 40°-60°; 10 ml) to give the title ester 1β-oxide (1.04 g, 67%), m.p. 181° to 182° (dec), [α]D + 164°, λmax. 265 nm (ε 7,900), νmax. (CHBr3) 3390 (NH), 1790 (azetidin-2-one), 1716 (CO2R), 1678 and 1510 (CONH) and 1050 cm-1 (S→O), τ (CDCl3 + 3 drops Me2SO-d6) 2.68 (5H,s; C6H5), 4.12 (1H,dd, J 9.5,4.5 Hz; C7 -H), 5.34 (1H,d, J 4.5 Hz; C6 -H), 6.37 (2H,s; C6H5CH2), 6.56 (2H,s; C2 -H2), 7.91 (3H,s; C3 -CH3), 8.47 (9H,s; CO2C(CH3)3) (Found: C, 60.0, 59.6; H, 6.1, 5.9; N, 6.7, 6.7; S, 7.8 C20H24N2O5S (404.5) requires C, 59.4; H, 6.0; N, 6.9; S, 7.9%).

1. customthe acetonitrile was removed in vacuo
2. additionWater (50 ml) and ethyl acetate (150 ml) were added
3. washthe organic phase was washed with water, 3% sodium hydrogen carbonate solution and water (50 ml of each),
4. customdried
5. customevaporated
6. dissolutionThe residual colourless oil was dissolved in methylene chloride (10 ml)
7. additionwas added dropwise
8. stirringThe solution was stirred at ca. 20° for 30 minutes
9. washThe organic phase was washed with water (50 ml)
10. customdried
11. customevaporated to a white gelatinous solid
12. custom(acetone-methylene chloride; 1:4) Rf 0.49, 0.80, which was purified by chromatography on Kieselgel G (50g)
13. washElution with acetonemethylene chloride (1:9)
14. customgave a pale yellow solid which
15. customwas crystallised from acetone-light petroleum, b.p. 40°-60° (1:1; 10 ml)