反应详情

Glacial acetic acid (5 ml) and N,N-dimethylformamide (125 ml) were added to a mixture of 2,2,2-trichloroethyl 3-bromomethyl-7β-formamidoceph-3-em-4-carboxylate, 1β-oxide (17.715 g, 25 mmole) and potassium acetate (12.25 g, ca. 125 mmole). The resulting mixture which darkened rapidly was stirred at ca. 20° for 1 hour when potassium iodide (30 g, 180 mmole) and acetyl chloride (13 ml, 0.183 mole) were added with stirring. The temperature of the reaction mixture rose to ca. 50°. After stirring for 15 minutes, M-sodium thiosulphate solution (30 ml) was added and the reaction mixture was diluted with methylene chloride (500 ml) and water (1 1) and shaken vigorously. The aqueous layer was re-extracted with methylene chloride (2 × 100 ml) and the combined organic phases were washed with water (300 ml) containing M-sodium thiosulphate solution (10 ml), and then water (3 × 300 ml). Each of these washings was acidic (pH 3) and contained suspended brown flocculent material. The dark brown methylene chloride solution was dried and filtered through a column of Kieselgel G (30 g) when much of the colour was retained. The eluate was evaporated and the residue was dissolved in ethyl acetate (100 ml), washed with water (2 × 200 ml) and evaporated to give the title ester as a brown foam (6.9 g, 64%), [α]D + 59° (CHCl3), λmax 265 nm (ε 6,800), νmax (CHBr3) 3430 (NH), 1790 (azetidin-2-one), 1745 (CO2R) and 1700 and 1510 cm-1 (CONH), τ (CDCl3) 1.76 (1H,s; CHO), 3.29 (1H,d, J 9.5 Hz; NH), 4.09 (1H,dd, J 9.5,5 Hz; C7 -H), 4.97 (1 H,d, J 5 Hz; C6 -H), 4.86, 5.16 (2H, Ab-q,J 14 Hz; C3 -CH2OCOCH3), 4.99, 5.25 (2H, AB-q, J 12 Hz; CH2CCl3), 6.36, 6.60 (2H, Ab-q, J 18 Hz; C2 -H2), 7.91 (3H,s; OCOCH3).

1. additionwere added
2. customrose to ca. 50°
3. stirringAfter stirring for 15 minutes
4. stirringshaken vigorously
5. extractionThe aqueous layer was re-extracted with methylene chloride (2 × 100 ml)
6. washthe combined organic phases were washed with water (300 ml)
7. additioncontaining M-sodium thiosulphate solution (10 ml)
8. dry with materialThe dark brown methylene chloride solution was dried
9. filtrationfiltered through a column of Kieselgel G (30 g) when much of the colour
10. customThe eluate was evaporated
11. dissolutionthe residue was dissolved in ethyl acetate (100 ml)
12. washwashed with water (2 × 200 ml)
13. customevaporated