N-Ethylpiperidine → (3S,4R)-3-[(1R)-1-(t-butyldimethylsilyloxy)ethyl]-4-[(1RS)-1-methyl-2-oxo-2-(2-thioxothiazolidin-3-yl)ethyl]-2-azetidinone

HRID 1461484Notes

Reaction equation

HRID 1461484 reaction equation
C(N1CCCCC1)C.[C:9]([N:13]1[CH2:17][CH2:16][S:15][C:14]1=[S:18])(=[O:12])[CH2:10][CH3:11].C(O[C@H:23]1[NH:26][C:25](=[O:27])[C@@H:24]1[C@H:28]([O:30][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32])[CH3:29])(=O)C.C(=O)(O)[O-].[Na+]>ClCCl.[Br-].[Zn+2].[Br-]>[Si:31]([O:30][C@@H:28]([C@@H:24]1[C@@H:23]([CH:10]([CH3:11])[C:9](=[O:12])[N:13]2[CH2:17][CH2:16][S:15][C:14]2=[S:18])[NH:26][C:25]1=[O:27])[CH3:29])([C:34]([CH3:35])([CH3:36])[CH3:37])([CH3:32])[CH3:33]

Participants

7

Reactant 4

HCID 13007N-EthylpiperidineHCID 516892Sodium BicarbonateHCID 10935078AzetidonHCID 114579872-Thiazolidinethione, 3-(1-oxopropyl)-

Product 1

HCID 57016647(3S,4R)-3-[(1R)-1-(t-butyldimethylsilyloxy)ethyl]-4-[(1RS)-1-methyl-2-oxo-2-(2-thioxothiazolidin-3-yl)ethyl]-2-azetidinoneYield 71.5%

Reagents, catalysts & solvents 2

HCID 10421208Zinc bromideCatalystHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-78 °C

Procedure

To a suspension of stannous trifluoromethanesulfonate (1.63 g) and N-ethylpiperidine (0.827 ml) in dichloromethane (12 ml) was added dropwise a solution of 3-propionyl-2-thioxothiazolidine (1.07 g) in dichloromethane (9 ml) at -78° C. under nitrogen atmosphere. After stirring at -78° C. for 30 minutes, a solution of (3R,4R)-4-acetoxy-3-[(1R)-1-(t-butyldimethylsilyloxy)ethyl]-2-azetidinone (0.876 g) and zinc bromide (1.37 g) in dichloromethane (3 ml) was added to the reaction mixture, and the reaction mixture was stirred at -20° C. for 15 hours. The reaction mixture was poured into aqueous sodium bicarbonate solution (30 ml) and the precipitated white mass was removed by passing through a layer of Celite. The organic layer was separated and washed with 10% aqueous sodium chloride solution (30 ml×2). The organic solution was dried over magnesium sulfate and evaporated. The residue was chromatographed on silica gel (21 g) eluting with a mixture of acetone and dichloromethane (2:98, V/V) to give (3S,4R)-3-[(1R)-1-(t-butyldimethylsilyloxy)ethyl]-4-[(1RS)-1-methyl-2-oxo-2-(2-thioxothiazolidin-3-yl)ethyl]-2-azetidinone (878 mg).

Workup

  1. stirringthe reaction mixture was stirred at -20° C. for 15 hours
  2. customthe precipitated white mass was removed
  3. customThe organic layer was separated
  4. washwashed with 10% aqueous sodium chloride solution (30 ml×2)
  5. dry with materialThe organic solution was dried over magnesium sulfate
  6. customevaporated
  7. customThe residue was chromatographed on silica gel (21 g)
  8. washeluting with a mixture of acetone and dichloromethane (2:98, V/V)

Sources & evidence

ORD record
ord-de8de6aa80484eb297612934272fb962
Source dataset
uspto-grants-1991_12
Patent number
US05075437

Reaction notes

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