反应详情

To an ice-cooled solution of 0.61 g of 5-bromoimidazo[5,1-b]thiazole in 6 ml of THF was added 3.2 ml of 1 M solution of ethyl magnesium bromide in THF. After stirring at room temperature for 2 hours, the mixture was cooled to −50° C., and a solution of 2.23 g of (3S,4R)-1-[(allyloxycarbonyl)(triphenylphosphoranylidene)methyl]-3-((1R)-1-t-butyldimethylsilyloxyethyl)-4-[(1R)-1-[(pyridin-2-yl)thiocarbonyl]ethyl]azetidin-2-one in 6 ml of THF was added. The mixture was stirred for 1 hour during which the temperature was raised up to 10° C. The reaction mixture was diluted with 12 ml of a saturated aqueous ammonium chloride solution, extracted with dichloromethane, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue thus obtained was purified by column chromatography on silica gel (hexane:ethyl acetate=3:2) to give 0.67 g of crude product. A 0.63 g portion of the crude product and a solution of 4.5 mg of hydroquinone in 7 ml of xylene were stirred under heating at 140° C. for 6 hours. The reaction mixture was diluted with 30 ml of ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate, and saturated aqueous saline in this sequence, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue thus obtained was purified by column chromatography on silica gel (hexane:ethyl acetate=2:1) to give 0.35 g of allyl (1S,5R,6S)-6-((1R)-1-t-butyldimethylsilyloxyethyl)-2-(imidazo[5,1-b]thiazol-5-yl)-1-methyl-1-carbapen-2-em-3-carboxylate.

1. temperaturethe mixture was cooled to −50° C.
2. stirringThe mixture was stirred for 1 hour during which the temperature
3. temperaturewas raised up to 10° C
4. extractionextracted with dichloromethane
5. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
6. customThe solvent was removed under reduced pressure
7. customthe residue thus obtained
8. customwas purified by column chromatography on silica gel (hexane:ethyl acetate=3:2)
9. customto give 0.67 g of crude product
10. temperatureunder heating at 140° C. for 6 hours
11. washwashed with saturated aqueous sodium hydrogen carbonate, and saturated aqueous saline in this sequence
12. dry with materialdried over anhydrous magnesium sulfate
13. customThe solvent was removed under reduced pressure
14. customthe residue thus obtained
15. customwas purified by column chromatography on silica gel (hexane:ethyl acetate=2:1)