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

HRID 2255670Notes

Reaction equation

HRID 2255670 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(N(CC)CC)C.Cl[Si](C)(C)C>O1CCCC1>[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

5

Reactant 3

HCID 6397ChlorotrimethylsilaneHCID 8471TriethylamineHCID 11054926ethyl (2S,3R)-2-aminomethyl-3-(t-butyldimethylsilyloxy)butanoate

Product 1

HCID 10130795(3S)-3-[(1R)-1-(t-butyldimethylsilyloxy)ethyl]azetidin-2-oneYield 47.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl (2S,3R)-2-aminomethyl-3-(t-butyldimethylsilyloxy)butanoate (1.38 g) and triethylamine (0.84 ml) in tetrahydrofuran (10 ml) was added dropwise chlorotrimethylsilane (0.76 ml) at room temperature. After stirring for 1 day, the precipitate was filtered and the filtrate was evaporated under reduced pressure. The residue was dissolved in tetrahydrofuran (50 ml) 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 layer was washed in turn with 1N hydrochloric acid in water (20 ml), saturated aqueous 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 (0.543 g).

Workup

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

Sources & evidence

ORD record
ord-a59797fbbe384e749d6da5f97a54efeb
Source dataset
uspto-grants-1993_08
Patent number
US05241064

Reaction notes

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