Citric Acid → (2S,3R)-1-t-butyldimethylsilyl-3-benzyl-4-oxo-2-azetidinecarboxylic acid

HRID 2413701Notes

Reaction equation

HRID 2413701 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[Si:13]([N:20]1[C:23](=[O:24])[CH2:22][C@H:21]1[C:25]([OH:27])=[O:26])([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14].[CH2:28](Br)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1.CCOCC.CCCCCC>[Si:13]([N:20]1[C:23](=[O:24])[C@H:22]([CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C@H:21]1[C:25]([OH:27])=[O:26])([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14]

Participants

9

Reactant 5

HCID 311Citric AcidHCID 7498Benzyl BromideHCID 7912DiisopropylamineHCID 10489602(2S)-1-[tert-Butyl(dimethyl)silyl]-4-oxoazetidine-2-carboxylic acidHCID 178418339Butyllithium

Product 1

HCID 13824878(2S,3R)-1-t-butyldimethylsilyl-3-benzyl-4-oxo-2-azetidinecarboxylic acidYield 67%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
0 °C

Procedure

In 6 ml of THF was dissolved 836.3 mg of diisopropylamine and the solution was cooled to 0° C. in a nitrogen atmosphere. To the solution was gradually added 5.2 ml of a n-hexane solution containing 530 mg of n-butyl lithium at 0° C. The mixture was stirred for 10 minutes at the same temperature. Then, a solution of 920 mg of (S)-1-t-butyldimethylsilyl-4-oxo-2-azetidinecarboxylic acid (1) in 8 ml of dry THF was added to the mixture at 0° C. followed by stirring at room temperature for 30 minutes. The solution was cooled to 0° C. and 820.8 mg of benzyl bromide was added to the solution. The mixture was then stirred at room temperature for 30 minutes. The solution was again cooled to 0° C. and a 10% citric acid solution was added thereto to render acidic. Ether was added to the mixture to separate from the aqueous phase. After the ethereal phase was dried, the solvent was removed by distillation to obtain 858 mg of (2S,3R)-1-t-butyldimethylsilyl-3-benzyl-4-oxo-2-azetidinecarboxylic acid (2) showing a melting point of 99°~102° C. as colorless crystals.

Workup

  1. stirringby stirring at room temperature for 30 minutes
  2. temperatureThe solution was cooled to 0° C.
  3. stirringThe mixture was then stirred at room temperature for 30 minutes
  4. temperatureThe solution was again cooled to 0° C.
  5. customto separate from the aqueous phase
  6. customAfter the ethereal phase was dried
  7. customthe solvent was removed by distillation

Sources & evidence

ORD record
ord-2531d4a5e89a47f89597347d0e796641
Source dataset
uspto-grants-1988_01
Patent number
US04719207

Reaction notes

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