反应详情

A solution of 2,2,2-trichloroethyl 3-bromomethyl-7β-formamidoceph-3-em-4-carboxylate, 1β-oxide (23.43 g, 50 mmole) in N,N-dimethylformamide (300 ml) was cooled to -5°, and condensed methanethiol (3.0 ml; ca. 56 mmole) was washed using precooled (-20°) N,N-dimethylformamide (50 ml). Triethylamine (7.0 ml, 50 mmole) was added and the solution was allowed to reach 15° over 30 min., then degassed at 15 nm. for a further 30 min. A small amount of crystallisation had taken place, so additional N,N-dimethylformamide (50 ml) was added and the resulting solution was cooled to -5°. Potassium iodide (16.6g, 100 mmole) was added, followed by acetyl chloride (7.2 ml, 100 mmole) over a period of 2 min. After ca. 2 min iodine was liberated. The cooling bath was withdrawn, and the solution stirred for 1 hr. and then refrigerated overnight at -17°. The solution was warmed to room temperature over 1 hr. and a solution of sodium metabisulphite (16.6g; ca. 75 mmole) in water (80 ml) was added. The pale-orange solution was poured into water (1500 ml) and extracted with methylene chloride (1000 ml, 500 ml, 250 ml). The combined extracts were washed successively with water, 2N-hydrochloric acid, water, 3% aqueous sodium hydrogen carbonate (100 ml. of each), dried, and evaporated to give an amber gum. This was dissolved in dry methanol (160 ml) and the solution was cooled in an ice-water bath. Phosphorus oxychloride (4.6 ml; 50 mmole) was added over 4 min. and after stirring for ca. 30 min. crystallisation of a white fluffy solid commenced. After a further 15 min. the mixture had set solid and was diluted with ether (75 ml), refrigerated for 1 hr. and the solid collected, washed with ether (100 ml) and dried to give the title hydrochloride (13.49g, 63.2%), m.p. 170°-172° (dec.) [α]D + 7.0° λmax. (MeOH) 272.5 nm (ε 6,630). Progressive concentration of the liquors provided three additional crops of an identical solid (1.87g, 1.82g, 0.19g; total 18.15%). All crops showed identical mobility on electrophoresis to that for the product described under Example D17 (iii).

1. washwas washed
2. custom(-20°) N,N-dimethylformamide (50 ml)
3. customdegassed at 15 nm
4. waitfor a further 30 min
5. customA small amount of crystallisation
6. additionwas added
7. temperaturethe resulting solution was cooled to -5°
8. customThe cooling bath was withdrawn
9. customrefrigerated overnight
10. customat -17°
11. extractionextracted with methylene chloride (1000 ml, 500 ml, 250 ml)
12. washThe combined extracts were washed successively with water, 2N-hydrochloric acid, water, 3% aqueous sodium hydrogen carbonate (100 ml
13. customof each), dried
14. customevaporated
15. customto give an amber gum
16. temperaturethe solution was cooled in an ice-water bath
17. stirringafter stirring for ca. 30 min.
18. customcrystallisation of a white fluffy solid commenced
19. waitAfter a further 15 min. the mixture had set
20. additionsolid and was diluted with ether (75 ml), refrigerated for 1 hr
21. customand the solid collected
22. washwashed with ether (100 ml)
23. customdried