Hexamethyldisilazane → (3S)-3-[(1R)-1-(t-butyldimethylsilyloxy)ethyl]azetidin-2-one

HRID 2255669Notes

Reaction equation

HRID 2255669 reaction equation
[NH2:1][CH2:2][C@@H:3]([C@H:9]([O:11][Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13])[CH3:10])[C:4](OCC)=[O:5].C[Si](C)(C)N[Si](C)(C)C>>[Si:12]([O:11][C@@H:9]([C@@H:3]1[CH2:2][NH:1][C:4]1=[O:5])[CH3:10])([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13]

Participants

3

Reactant 2

HCID 13838HexamethyldisilazaneHCID 11054926ethyl (2S,3R)-2-aminomethyl-3-(t-butyldimethylsilyloxy)butanoate

Product 1

HCID 10130795(3S)-3-[(1R)-1-(t-butyldimethylsilyloxy)ethyl]azetidin-2-oneYield 73.2%

Conditions

Temperature
70 °C

Procedure

A mixture of ethyl (2S,3R)-2-aminomethyl-3-(t-butyldimethylsilyloxy)butanoate (1.38 g) and 1,1,1,3,3,3-hexamethyldisilazane (1.58 ml) was stirred at 70° C. for 15 hours, and then concentrated under reduced pressure. The residue was dissolved in 50 ml of tetrahydrofuran and 1.1N t-butylmagnesium chloride in tetrahydrofuran (15 ml) was added dropwise thereto at room temperature. After stirring for 30 minutes, the reaction mixture was quenched with water (10 ml), and diluted with ethyl acetate (50 ml) and 1N hydrochloric acid in water (20 ml). The aqueous layer was separated and extracted twice with ethyl acetate (25 ml×2) and the combined organic layers were washed in turn with 1N hydrochloric acid in water (20 ml), saturated sodium bicarbonate (20 ml), water (20 ml) and brine (20 ml), dried over magnesium sulfate and evaporated under reduced pressure. The residue was column-chromatographed on silica gel (hexane-ethyl acetate=3:1) to give (3S)-3-[ (1R)-1-(t-butyldimethylsilyloxy)ethyl]-azetidin-2-one (0.841 g).

Workup

  1. concentrationconcentrated under reduced pressure
  2. dissolutionThe residue was dissolved in 50 ml of tetrahydrofuran
  3. addition1.1N t-butylmagnesium chloride in tetrahydrofuran (15 ml) was added dropwise
  4. customat room temperature
  5. stirringAfter stirring for 30 minutes
  6. customthe reaction mixture was quenched with water (10 ml)
  7. additiondiluted with ethyl acetate (50 ml) and 1N hydrochloric acid in water (20 ml)
  8. customThe aqueous layer was separated
  9. extractionextracted twice with ethyl acetate (25 ml×2)
  10. washthe combined organic layers were washed in turn with 1N hydrochloric acid in water (20 ml), saturated sodium bicarbonate (20 ml), water (20 ml) and brine (20 ml)
  11. dry with materialdried over magnesium sulfate
  12. customevaporated under reduced pressure
  13. customThe residue was column-chromatographed on silica gel (hexane-ethyl acetate=3:1)

Sources & evidence

ORD record
ord-ec7976cfac264b11adf6f39b4f1ffdb4
Source dataset
uspto-grants-1993_08
Patent number
US05241064

Reaction notes

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