反应详情

To a stirred solution of 1646 g. of 6,6-dibromo-2,2-dimethyl-(5R)penam-3α-carboxylic acid in 10.1 liters of N,N-dimethylacetamide was added 709 ml. of triethylamine during 10 minutes at ca. 0° C. The temperature was adjusted to 10° C., and 602 ml. of benzyl bromide was added during 4 minutes. To the reaction mixture was then added 941 g. of 4A molecular sieves, and then the reaction mixture was stirred overnight without external cooling. At this point, the reaction mixture was filtered and the filtrate was added to a mixture of 44 liters of ice-water and 14 liters of ethyl acetate. The pH of the aqueous phase was adjusted to 2.0 using 6 N hydrochloric acid, and the layers were separated. The aqueous layer was extracted with further ethyl acetate and the combined ethyl acetate solutions were washed sequentially with 14 liters of saturated, aqueous sodium bicarbonate and 14 liters of saturated, aqueous sodium chloride. The ethyl acetate solution was dried (Na2SO4), and then it was evaporated in vacuo at 25° C. The residue was dissolved in 5.5 liters of isopropyl alcohol at 60° C., and then the isopropyl alcohol solution was cooled slowly with stirring. The solid which precipitated was recovered by filtration, washed with cold isopropyl alcohol and then air dried. This afforded 1777 g. (85% yield) of the title product. The NMR spectrum (CDCl3) showed absorptions at 1.40 (s, 3H), 1.55 (s, 3H), 4.55 (s, 1H), 5.20 (s, 2H), 5.75 (s, 1H) and 7.35 (s, 5H) ppm.

1. customwas adjusted to 10° C.
2. additionTo the reaction mixture was then added 941 g
3. filtrationAt this point, the reaction mixture was filtered
4. additionthe filtrate was added to a mixture of 44 liters of ice-water and 14 liters of ethyl acetate
5. customthe layers were separated
6. extractionThe aqueous layer was extracted with further ethyl acetate
7. washthe combined ethyl acetate solutions were washed sequentially with 14 liters of saturated, aqueous sodium bicarbonate and 14 liters of saturated, aqueous sodium chloride
8. dry with materialThe ethyl acetate solution was dried (Na2SO4)
9. customit was evaporated in vacuo at 25° C
10. dissolutionThe residue was dissolved in 5.5 liters of isopropyl alcohol at 60° C.
11. temperaturethe isopropyl alcohol solution was cooled slowly
12. customThe solid which precipitated
13. filtrationwas recovered by filtration
14. washwashed with cold isopropyl alcohol
15. customair dried