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

HRID 1464723Notes

Reaction equation

HRID 1464723 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[C:13]([S:17][CH3:18])(=[S:16])[CH2:14][CH3:15].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>O1CCCC1.CCCCCC.CC(C)[O-].CC(C)[O-].CC(C)[O-].Cl[Ti+3]>[Si:31]([O:30][C@@H:28]([C@@H:24]1[C@@H:23]([C@H:14]([C:13]([S:17][CH3:18])=[S:16])[CH3:15])[NH:26][C:25]1=[O:27])[CH3:29])([C:34]([CH3:35])([CH3:36])[CH3:37])([CH3:32])[CH3:33]

Participants

8

Reactant 4

HCID 7912DiisopropylamineHCID 223580Methyl propanedithioateHCID 10935078AzetidonHCID 178418339Butyllithium

Product 1

HCID 57309161(3S,4S)-3-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-4-[(1R)-1-[(methylthio)thiocarbonyl}ethyl]-2-oxoazetidineYield 58.2%

Reagents, catalysts & solvents 3

HCID 11673339ChlorotitaniumtriisopropoxideCatalystHCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of diisopropylamine (152 mg) in anhydrous tetrahydrofuran (2 ml) cooled to 0° C. was added a 1.56M solution of n-butyllithium in n-hexane (0.95 ml). After stirring for 30 minutes at 0° C., the solution was cooled to -78° C. and methyl dithiopropionate (120 mg) and a 1M solution of chlorotitanium triisopropoxide in hexane (4.0 ml) were added successively thereto. The mixture was warmed to -40° C. and (3R,4R)-4-acetoxy-3-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-2-oxoazetidine (287 mg) was added thereto. The solution was allowed to warm to 0° C., quenched by 1N hydrochrolic acid, and extracted with diethyl ether. The organic layer was washed with brine, dried, and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (10% diethyl ether-hexane) to afford a mixture (202 mg) of (3S,4S)-3-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-4 -[(1R)-1-[(methylthio)thiocarbonyl}ethyl]-2-oxoazetidine and (3S,4S)-3-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-4-[(1S)-1-{(methylthio)thiocarbonyl}ethyl]-2-oxoazetidine. Recrystallization of the product obtained above from n-hexane gave (3S,4S)-3-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-4-[(1R)-1-{(methylthio)thiocarbonyl}ethyl]-2-oxoazetidine as a yellow needle.

Workup

  1. temperaturethe solution was cooled to -78° C.
  2. temperatureThe mixture was warmed to -40° C.
  3. temperatureto warm to 0° C.
  4. customquenched by 1N hydrochrolic acid
  5. extractionextracted with diethyl ether
  6. washThe organic layer was washed with brine
  7. customdried
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by flash chromatography on silica gel (10% diethyl ether-hexane)

Sources & evidence

ORD record
ord-88ffb50b26f04ca5bdb257093b834648
Source dataset
uspto-grants-1994_04
Patent number
US05306816

Reaction notes

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