Imidazole → (S)-2-(tert-butyldimethylsilyloxy)-1-(pyrrolidin-1-yl)propan-1-one

HRID 2279467Notes

Reaction equation

HRID 2279467 reaction equation
[OH:1][C@@H:2]([CH3:10])[C:3]([N:5]1[CH2:9][CH2:8][CH2:7][CH2:6]1)=[O:4].N1C=CN=C1.[C:16]([Si:20](Cl)([CH3:22])[CH3:21])([CH3:19])([CH3:18])[CH3:17].O>CN(C1C=CN=CC=1)C.CN(C=O)C>[Si:20]([O:1][C@@H:2]([CH3:10])[C:3]([N:5]1[CH2:9][CH2:8][CH2:7][CH2:6]1)=[O:4])([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:22])[CH3:21]

Participants

7

Reactant 4

HCID 795ImidazoleHCID 962WaterHCID 28928tert-Butyldimethylsilyl chlorideHCID 11051776(2S)-2-hydroxy-1-(1-pyrrolidinyl)-1-propanone

Product 1

HCID 11807344(S)-2-(tert-butyldimethylsilyloxy)-1-(pyrrolidin-1-yl)propan-1-oneYield 77.1%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of 108 (41.1 g, 287.0 mmol), imidazole (29.31 g, 430.6 mmol), and DMAP (3.507 g, 28.70 mmol) in DMF (100 mL) was added slowly tert-butylchlorodimethylsilane (54.08 g, 358.8 mmol) and the reaction was stirred at RT for 18 h. Water was added and mixture was extracted with Et2O. The organic layer was dried, filtered, and concentrated. The resulting residue was purified by passing through a SiO2 plug eluting with an EtOAc/hexane gradient (10 to 50% EtOAc) to afford 56.93 g (77.04%) of (S)-2-(tert-butyldimethylsilyloxy)-1-(pyrrolidin-1-yl)propan-1-one (110).

Workup

  1. extractionmixture was extracted with Et2O
  2. customThe organic layer was dried
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe resulting residue was purified
  6. washeluting with an EtOAc/hexane gradient (10 to 50% EtOAc)

Sources & evidence

ORD record
ord-2924cbacd0714900949f796d8899a9d2
Source dataset
uspto-grants-2015_09
Patent number
US09133187B2

Reaction notes

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