Citric Acid → (3S,4R)-3-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-4-[1-methyl-2-[7-(pyridin-3-yl)triethylsilyloxymethylimidazo[5,1-b]thiazol-2-yl]-2-oxoethyl]azetidin-2-one

HRID 2113292

Reaction equation

HRID 2113292 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[Br-].[Li+].[C:13]([C:17]1[S:21][C:20]2=[C:22]([C:25]3[CH:26]=[N:27][CH:28]=[CH:29][CH:30]=3)[N:23]=[CH:24][N:19]2[C:18]=1[CH2:31][O:32][Si:33]([CH2:38][CH3:39])([CH2:36][CH3:37])[CH2:34][CH3:35])(=[O:16])[CH2:14][CH3:15].C(O[C@H:44]1[NH:47][C:46](=[O:48])[C@H:45]1[C@H:49]([O:51][Si:52]([C:55]([CH3:58])([CH3:57])[CH3:56])([CH3:54])[CH3:53])[CH3:50])(=O)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1>[Si:52]([O:51][C@@H:49]([C@@H:45]1[C@@H:44]([CH:14]([CH3:15])[C:13]([C:17]2[S:21][C:20]3=[C:22]([C:25]4[CH:26]=[N:27][CH:28]=[CH:29][CH:30]=4)[N:23]=[CH:24][N:19]3[C:18]=2[CH2:31][O:32][Si:33]([CH2:34][CH3:35])([CH2:38][CH3:39])[CH2:36][CH3:37])=[O:16])[NH:47][C:46]1=[O:48])[CH3:50])([C:55]([CH3:56])([CH3:57])[CH3:58])([CH3:53])[CH3:54]

Participants

7

Reactant 5

HCID 311Citric AcidHCID 82050Lithium BromideHCID 2733832Lithium HexamethyldisilazideHCID 13073890(3R,4R)-4-Acetoxy-3-((R)-(tert-butyldimethylsilyloxy)ethyl)-2-azetidinoneHCID 688215852-Propionyl-7-(pyridin-3-yl)triethylsilyloxymethylimidazo[5,1-b]thiazole

Product 1

HCID 68823830(3S,4R)-3-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-4-[1-methyl-2-[7-(pyridin-3-yl)triethylsilyloxymethylimidazo[5,1-b]thiazol-2-yl]-2-oxoethyl]azetidin-2-oneYield 53.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent4×

Conditions

Temperature
-78 °C

Procedure

A 1 M tetrahydrofuran solution (5.2 ml) of lithium bistrimethylsilylamide was added to a solution of 2.05 g of lithium bromide in 10 ml of tetrahydrofuran under an argon atmosphere, and the mixture was cooled to −78° C. A solution of 0.95 g of 2-propionyl-7-(pyridin-3-yl)triethylsilyl oxymethylimidazo[5,1-b]thiazole in 4.7 ml of tetrahydrofuran was added thereto, and the mixture was stirred at that temperature for one hr. A solution of 0.81 g of (3S,4R)-4-acetoxy-3-[(1R)-1-tert-butyldimethylsilyloxyethyl]azetidin-2-one in 3.8 ml of tetrahydrofuran was added thereto, and the mixture was stirred at that temperature for 2 hr. A 10% aqueous citric acid solution was added to the reaction mixture to stop the reaction, and the reaction mixture was extracted with ethyl acetate. The extract was washed with a saturated aqueous sodium bicarbonate solution and saturated brine in that order and was then dried over anhydrous magnesium sulfate. The extract was then concentrated by removing the solvent, and the concentrate was purified by column chromatography on silica gel (5 to 10% methanol/methylene chloride) to give 0.80 g of a crude product of (3S,4R)-3-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-4-[1-methyl-2-[7-(pyridin-3-yl)triethylsilyloxymethylimidazo[5,1-b]thiazol-2-yl]-2-oxo ethyl]azetidin-2-one.

Workup

  1. stirringthe mixture was stirred at that temperature for 2 hr
  2. customthe reaction
  3. extractionthe reaction mixture was extracted with ethyl acetate
  4. washThe extract was washed with a saturated aqueous sodium bicarbonate solution and saturated brine in that order
  5. dry with materialwas then dried over anhydrous magnesium sulfate
  6. concentrationThe extract was then concentrated
  7. customby removing the solvent
  8. customthe concentrate was purified by column chromatography on silica gel (5 to 10% methanol/methylene chloride)

Sources & evidence

ORD record
ord-f5eef76896e1463a945614f0f37fda03
Source dataset
uspto-grants-2009_04
Patent number
US07524951B2

Linked notes

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