5-Bromoimidazo[5,1-b]thiazole → 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

HRID 382630노트

반응식

HRID 382630 반응식
Br[C:2]1[N:9]2[C:5]([S:6][CH:7]=[CH:8]2)=[CH:4][N:3]=1.C([Mg]Br)C.[CH2:14]([O:17][C:18]([C:20](=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[N:21]1[C@@H:24]([C@H:25]([C:27](C2C=CC=CN=2)=S)[CH3:26])[C@@H:23]([C@H:35]([O:37][Si:38]([C:41]([CH3:44])([CH3:43])[CH3:42])([CH3:40])[CH3:39])[CH3:36])[C:22]1=[O:45])=[O:19])[CH:15]=[CH2:16]>C1COCC1.[Cl-].[NH4+].C1(C)C(C)=CC=CC=1.C(OCC)(=O)C.C1(C=CC(O)=CC=1)O>[Si:38]([O:37][C@@H:35]([C@H:23]1[C:22](=[O:45])[N:21]2[C:20]([C:18]([O:17][CH2:14][CH:15]=[CH2:16])=[O:19])=[C:26]([C:2]3[N:9]4[C:5]([S:6][CH:7]=[CH:8]4)=[CH:4][N:3]=3)[C@H:25]([CH3:27])[C@H:24]12)[CH3:36])([C:41]([CH3:44])([CH3:43])[CH3:42])([CH3:39])[CH3:40]

참가 물질

9

반응물 3

HCID 183598575-Bromoimidazo[5,1-b]thiazoleHCID 88175931(3S,4R)-1-[(allyloxycarbonyl)(triphenylphosphoranylidene)methyl]-3-((1R)-1-t-butyldimethylsilyloxyethyl)-4-[(1R)-1-[(pyridin-2-yl)thiocarbonyl]ethyl]azetidin-2-oneHCID 178418443HCID 178418443, 화합물

생성물 1

HCID 131722905allyl (1S,5R,6S)-6-((1R)-1-t-butyldimethylsilyloxyethyl)-2-(imidazo[5,1-b]thiazol-5-yl)-1-methyl-1-carbapen-2-em-3-carboxylate수율 23.9%

시약·촉매·용매 5

HCID 785Hydroquinone촉매HCID 7237O-Xylene용매HCID 8028Tetrahydrofuran용매3회HCID 8857Ethyl Acetate용매HCID 25517Ammonium Chloride용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-5f9768380f484ddd8cde9e11dc00dfdb
출처 데이터셋
uspto-grants-2001_10
특허 번호
US06310056B1

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