4-Methoxybenzylamine → (3S)-3-[(1R)-1-(t-butyldimethylsilyloxy)ethyl]-1-(4-methoxybenzyl)azetidin-2-one

HRID 2255662Notes

Reaction equation

HRID 2255662 reaction equation
[C:1]([Si:5]([CH3:15])([CH3:14])[O:6][CH:7]([C:9](=[CH2:13])[C:10]([O-:12])=O)[CH3:8])([CH3:4])([CH3:3])[CH3:2].[CH3:16][O:17][C:18]1[CH:25]=[CH:24][C:21]([CH2:22][NH2:23])=[CH:20][CH:19]=1>CO>[Si:5]([O:6][C@@H:7]([C@@H:9]1[CH2:13][N:23]([CH2:22][C:21]2[CH:24]=[CH:25][C:18]([O:17][CH3:16])=[CH:19][CH:20]=2)[C:10]1=[O:12])[CH3:8])([C:1]([CH3:2])([CH3:3])[CH3:4])([CH3:15])[CH3:14]

Participants

4

Reactant 2

HCID 754524-MethoxybenzylamineHCID 19099242HCID 19099242, compound

Product 1

HCID 54758409(3S)-3-[(1R)-1-(t-butyldimethylsilyloxy)ethyl]-1-(4-methoxybenzyl)azetidin-2-oneYield 66.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of ethyl (2-[1-(t-butyldimethyl-silyloxy)ethyl]acrylate (5 g) in methanol (100 ml) was added 4-methoxybenzylamine (2.65 g) at room temperature. After two days, the solvent was evaporated and the residual methanol was azeotropically removed using toluene. To the residual product was added tetrahydrofuran (387 ml) and the solution was stirred at room temperature. To this solution was added dropwise mesitylmagnesium bromide in tetrahydrofuran (1M, 31 ml) at room temperature. After stirring for 30 minutes, the reaction mixture was quenched with water and evaporated. The aqueous layer was extracted twice with ethyl acetate. The combined organic layers were washed with 1N hydrochloric acid, saturated aqueous sodium hydrogencarbonate, water and an aqueous sodium chloride in turn, and then dried over magnesium sulfate. The resultant solution was evaporated and the residue was column-chromatographed on silica gel (eluent : a mixture of hexane and ethyl acetate, 3:1) to give (3S*)-3-[(1R*)-1-(t-butyldimethylsilyloxy)ethyl]-1-(4-methoxybenzyl)azetidin-2-one (4.5 g).

Workup

  1. customthe solvent was evaporated
  2. customthe residual methanol was azeotropically removed
  3. additionTo the residual product was added tetrahydrofuran (387 ml)
  4. additionTo this solution was added dropwise mesitylmagnesium bromide in tetrahydrofuran (1M, 31 ml) at room temperature
  5. stirringAfter stirring for 30 minutes
  6. customthe reaction mixture was quenched with water
  7. customevaporated
  8. extractionThe aqueous layer was extracted twice with ethyl acetate
  9. washThe combined organic layers were washed with 1N hydrochloric acid, saturated aqueous sodium hydrogencarbonate, water
  10. dry with materialan aqueous sodium chloride in turn, and then dried over magnesium sulfate
  11. customThe resultant solution was evaporated
  12. customthe residue was column-chromatographed on silica gel (eluent
  13. additiona mixture of hexane and ethyl acetate, 3:1)

Sources & evidence

ORD record
ord-d81d5123fdfa4cc6b29c52931f88ef2f
Source dataset
uspto-grants-1993_08
Patent number
US05241064

Reaction notes

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