N-Ethylpiperidine → (3s,4r)-3-[(1r)-1-(Tert-butyldimethylsilyloxy)ethyl]-4-[(1r)-1-methyl-2-[7-dimethoxymethyl(pyridin-3-yl)imidazo[5,1-b]thiazol-2-yl]-2-oxoethyl]azetidin-2-one

HRID 2113294

Reaction equation

HRID 2113294 reaction equation
FC(F)(F)S([O-])(=O)=O.[Sn+2].FC(F)(F)S([O-])(=O)=O.C([C:22]1[S:26][C:25]2=[C:27]([C:30]3[CH:31]=[N:32][CH:33]=[CH:34][CH:35]=3)[N:28]=[CH:29][N:24]2[C:23]=1[CH:36]([O:39][CH3:40])[O:37][CH3:38])(=O)CC.C(O[C@H:45]1[NH:48][C:47](=[O:49])[C@H:46]1[C@H:50]([O:52][Si:53]([C:56]([CH3:59])([CH3:58])[CH3:57])([CH3:55])[CH3:54])[CH3:51])(=O)C.[C:60](=[O:63])(O)[O-].[Na+].[CH2:65](N1CCCCC1)[CH3:66]>C(Cl)Cl>[Si:53]([O:52][C@@H:50]([C@@H:46]1[C@@H:45]([C@@H:65]([CH3:66])[C:60]([C:25]2[S:26][C:22]3=[C:23]([CH:36]([O:37][CH3:38])[O:39][CH3:40])[N:24]=[CH:29][N:28]3[C:27]=2[C:30]2[CH:31]=[N:32][CH:33]=[CH:34][CH:35]=2)=[O:63])[NH:48][C:47]1=[O:49])[CH3:51])([C:56]([CH3:57])([CH3:58])[CH3:59])([CH3:54])[CH3:55]

Participants

7

Reactant 5

HCID 13007N-EthylpiperidineHCID 516892Sodium BicarbonateHCID 2776843Tin(II) trifluoromethanesulfonateHCID 13073890(3R,4R)-4-Acetoxy-3-((R)-(tert-butyldimethylsilyloxy)ethyl)-2-azetidinoneHCID 688211002-Propionyl-7-(pyridin-3-yl)dimethoxymethylimidazo[5,1-b]thiazole

Product 1

HCID 68821587(3s,4r)-3-[(1r)-1-(Tert-butyldimethylsilyloxy)ethyl]-4-[(1r)-1-methyl-2-[7-dimethoxymethyl(pyridin-3-yl)imidazo[5,1-b]thiazol-2-yl]-2-oxoethyl]azetidin-2-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-20 °C

Procedure

Methylene chloride (2 ml) was added to 0.69 g of tin(II) trifluoromethanesulfonate under an argon atmosphere, and the mixture was cooled to −20° C. A solution of 0.25 g of 2-propionyl-7-(pyridin-3-yl)dimethoxymethylimidazo[5,1-b]thiazole in 1.5 ml of methylene chloride and 0.12 ml of N-ethylpiperidine were added thereto, and the mixture was stirred for 2 hr. A solution of 0.14 g of (3S,4R)-4-acetoxy-3-[(1R)-1-tert-butyldimethylsilyloxyethyl]azetidin-2-one in 1 ml of methylene chloride was added at 0° C., and the mixture was stirred at room temperature for one hr. A saturated aqueous sodium bicarbonate solution was added to the reaction mixture to stop the reaction, and the reaction mixture was extracted with ethyl acetate. The organic layer was washed with a 5% aqueous sodium bicarbonate solution and a 20% aqueous sodium chloride solution in that order and was dried over anhydrous magnesium sulfate. The solvent was removed by evaporation, and the residue was analyzed by HPLC (Cosmosil 5C18-MS, 4.6×150 mm, a 70% aqueous acetonitrile solution). As a result, it was found that the yield of (3S,4R)-3-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-4-[(1R)-1-methyl-2-[7-dimethoxy(pyridin-3-yl)methylimidazo[5,1-b]thiazol-2-yl]-2-oxoethyl]azetidin-2-one was 45 mg. The results of analysis by NMR were in agreement with the results of analysis in Example 18.

Workup

  1. stirringthe mixture was stirred at room temperature for one hr
  2. customthe reaction
  3. extractionthe reaction mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with a 5% aqueous sodium bicarbonate solution
  5. dry with materiala 20% aqueous sodium chloride solution in that order and was dried over anhydrous magnesium sulfate
  6. customThe solvent was removed by evaporation
  7. customThe results of analysis by NMR
  8. customresults of analysis in Example 18

Sources & evidence

ORD record
ord-5cf5e59e24614214827efd28054a0ffc
Source dataset
uspto-grants-2009_04
Patent number
US07524951B2

Linked notes

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