Imidazole → Methyl (R)-2-[(tert-butyldimethylsilyl)oxy]-2-(3-chlorophenyl)acetate

HRID 1682761Notes

Reaction equation

HRID 1682761 reaction equation
[Si:1](Cl)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Cl:9][C:10]1[CH:11]=[C:12]([CH:19]=[CH:20][CH:21]=1)[C@@H:13]([OH:18])[C:14]([O:16][CH3:17])=[O:15].N1C=CN=C1>CN(C)C=O>[Si:1]([O:18][C@H:13]([C:12]1[CH:19]=[CH:20][CH:21]=[C:10]([Cl:9])[CH:11]=1)[C:14]([O:16][CH3:17])=[O:15])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 15606324(R)-Methyl 2-(3-chlorophenyl)-2-hydroxyacetate

Product 1

HCID 54113343Methyl (R)-2-[(tert-butyldimethylsilyl)oxy]-2-(3-chlorophenyl)acetate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 31.6 g of t-butyldimethylsilyl chloride in 200 ml of dimethylformamide was added dropwise, whilst ice-cooling, to a solution of 28 g of methyl (R)-3-chloromandelate (prepared as described in Preparation 47) and 28.5 g of imidazole in 300 ml of dimethylformamide, and the resulting mixture was stirred at the same temperature for 30 minutes, after which it was allowed to stand overnight at 40° C. At the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure, and the residue was mixed with water and ethyl acetate. The ethyl acetate layer was separated and dried over anhydrous sodium sulfate, and then the solvent was removed by distillation under reduced pressure. The resulting residue was purified by column chromatography through silica gel, using a 1:15 by volume mixture of ethyl acetate and hexane as the eluent, to give the title compound as crystals, melting at 36°-38° C. [α]D23 -39.1° (c=1.014, chloroform)

Workup

  1. waitto stand overnight at 40° C
  2. concentrationAt the end of this time, the reaction mixture was concentrated by evaporation under reduced pressure
  3. additionthe residue was mixed with water and ethyl acetate
  4. customThe ethyl acetate layer was separated
  5. dry with materialdried over anhydrous sodium sulfate
  6. customthe solvent was removed by distillation under reduced pressure
  7. customThe resulting residue was purified by column chromatography through silica gel
  8. additionby volume mixture of ethyl acetate and hexane as the eluent

Sources & evidence

ORD record
ord-0a7d4e57035f4f18b183dae097090fe5
Source dataset
uspto-grants-1997_06
Patent number
US05635534

Reaction notes

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