Imidazole → (S)-6-((S)-1-(tert-butyldimethylsilyloxy)ethyl)-2,2-dimethylpiperidin-4-one

HRID 1027155Notes

Reaction equation

HRID 1027155 reaction equation
[OH:1][C@H:2]([C@H:4]1[NH:9][C:8]([CH3:11])([CH3:10])[CH2:7][C:6](=[O:12])[CH2:5]1)[CH3:3].N1C=CN=C1.[CH3:18][C:19]([Si:22](Cl)([CH3:24])[CH3:23])([CH3:21])[CH3:20]>CN(C=O)C.O>[Si:22]([O:1][C@H:2]([C@H:4]1[NH:9][C:8]([CH3:11])([CH3:10])[CH2:7][C:6](=[O:12])[CH2:5]1)[CH3:3])([C:19]([CH3:21])([CH3:20])[CH3:18])([CH3:24])[CH3:23]

Participants

6

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 86710548HCID 86710548, compound

Product 1

HCID 86710549(S)-6-((S)-1-(tert-butyldimethylsilyloxy)ethyl)-2,2-dimethylpiperidin-4-oneYield 35.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of (S)-6-((S)-1-hydroxyethyl)-2,2-dimethylpiperidin-4-one (0.11 g, 0.64 mmol) in DMF (3 mL) were added imidazole (0.13 g, 1.93 mmol) and TBSCl (0.14 g, 0.96 mmol). The mixture was stirred overnight. The reaction mixture was diluted with water (10 mL) and extracted with EtOAc (20 mL). The extract was washed with brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by column chromatography (EtOAc/Heptane) to afford 65 mg (35%) of (S)-6-((S)-1-(tert-butyldimethylsilyloxy)ethyl)-2,2-dimethylpiperidin-4-one: 1H NMR (400 MHz, CHLOROFORM-d) δ 3.99 (dq, J=6.3, 2.8 Hz, 1H), 2.96-3.04 (m, 1H), 2.21-2.32 (m, 3H), 2.13 (d, J=13.1 Hz, 1H), 1.26 (s, 3H), 1.12 (d, J=6.1 Hz, 3H), 1.05 (s, 3H), 0.91 (s, 9H), 0.12 (s, 3H), 0.09 (s, 3H).

Workup

  1. extractionextracted with EtOAc (20 mL)
  2. washThe extract was washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by column chromatography (EtOAc/Heptane)

Sources & evidence

ORD record
ord-b4ae68a9ad4241ceb2e7cb23b27df9a5
Source dataset
uspto-grants-2014_05
Patent number
US08729263B2

Reaction notes

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