Hydrochloric Acid → (3S,4S)-3-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-4-[(1R)-1-[(methylthio)thiocarbonyl}ethyl]-2-oxoazetidine

HRID 1464722

Reaction equation

HRID 1464722 reaction equation
C(N(CC)CC)C.[C:8]([S:12][CH3:13])(=[S:11])[CH2:9][CH3:10].C(O[C@H:18]1[NH:21][C:20](=[O:22])[C@@H:19]1[C@H:23]([O:25][Si:26]([C:29]([CH3:32])([CH3:31])[CH3:30])([CH3:28])[CH3:27])[CH3:24])(=O)C.Cl>C(#N)C.[Cl-].[Zn+2].[Cl-].ClCCl>[Si:26]([O:25][C@@H:23]([C@@H:19]1[C@@H:18]([C@H:9]([C:8]([S:12][CH3:13])=[S:11])[CH3:10])[NH:21][C:20]1=[O:22])[CH3:24])([C:29]([CH3:30])([CH3:31])[CH3:32])([CH3:27])[CH3:28]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 223580Methyl propanedithioateHCID 10935078Azetidon

Product 1

HCID 57309161(3S,4S)-3-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-4-[(1R)-1-[(methylthio)thiocarbonyl}ethyl]-2-oxoazetidineYield 69.5%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 6342AcetonitrileSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of anhydrous zinc chloride (45.3 g) in acetonitrile (450 ml) cooled to 0° C. was added triethylamine (101 g). After stirring for 30 minutes at 0° C., the solution was cooled to -35° C. and a mixture of methyl dithiopropionate (20.0 g) and (3R,4R)-4-acetoxy-3-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-2-oxoazetidine (23.9 g) in acetonitrile (90 ml) was added thereto. The reaction mixture was stirred at -20° C. for 2 hours, warmed to 0° C., and additionally stirred for 30 minutes at 0° C. The mixture was poured into a stirred mixture of dichloromethane (800 ml) and 1N hydrochloric acid (1000 ml). The organic layer was separated, washed with water, aqueous sodium bicarbonate solution and brine, and dried. The solution was concentrated under reduced pressure and the solid residue was washed with n-hexane to afford (3S,4S)-3-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-4-[(1R)-1-{(methylthio)thiocarbonyl}ethyl]-2-oxoazetidine (20.1 g) as a yellow crystal.

Workup

  1. temperaturethe solution was cooled to -35° C.
  2. additionwas added
  3. stirringThe reaction mixture was stirred at -20° C. for 2 hours
  4. temperaturewarmed to 0° C.
  5. stirringadditionally stirred for 30 minutes at 0° C
  6. customThe organic layer was separated
  7. washwashed with water, aqueous sodium bicarbonate solution and brine
  8. customdried
  9. concentrationThe solution was concentrated under reduced pressure
  10. washthe solid residue was washed with n-hexane

Sources & evidence

ORD record
ord-8ebceed7fa414a45907d86cc7076cf97
Source dataset
uspto-grants-1994_04
Patent number
US05306816

Linked notes

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