Imidazole → (R)-3-(tert-butyldimethylsilyloxy)-1-(2-nitro-4-(trifluoromethyl)phenyl)piperidine

HRID 1042641Notes

Reaction equation

HRID 1042641 reaction equation
[N+:1]([C:4]1[CH:9]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:7]=[CH:6][C:5]=1[N:14]1[CH2:19][CH2:18][CH2:17][C@@H:16]([OH:20])[CH2:15]1)([O-:3])=[O:2].N1C=CN=C1.[Si:26](Cl)([C:29]([CH3:32])([CH3:31])[CH3:30])([CH3:28])[CH3:27].CCOCC>CN(C=O)C>[Si:26]([O:20][C@@H:16]1[CH2:17][CH2:18][CH2:19][N:14]([C:5]2[CH:6]=[CH:7][C:8]([C:10]([F:11])([F:12])[F:13])=[CH:9][C:4]=2[N+:1]([O-:3])=[O:2])[CH2:15]1)([C:29]([CH3:32])([CH3:31])[CH3:30])([CH3:28])[CH3:27]

Participants

6

Reactant 4

HCID 795ImidazoleHCID 3283Diethyl EtherHCID 28928tert-Butyldimethylsilyl chloride2×HCID 7449941(R)-1-(2-nitro-4-(trifluoromethyl)phenyl)piperidin-3-ol

Product 1

HCID 68463512(R)-3-(tert-butyldimethylsilyloxy)-1-(2-nitro-4-(trifluoromethyl)phenyl)piperidine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (R)-1-(2-nitro-4-(trifluoromethyl)phenyl)piperidin-3-ol (3.35 g, 11.5 mmol) and imidazole (1.02 g, 15.0 mmol) in DMF at ambient temperature under nitrogen was added tert-butyldimethylsilylchloride (1.91 g, 12.7 mmol). The reaction was allowed to stir for 24 h, at which point additional 0.3 g tert-butyldimethylsilylchloride was added. The reaction was allowed to stir for an additional 14 h, and was then poured into Et2O/saturated aqueous NaHCO3. The organic layer was washed 2× H2O, 1× brine, dried over anhydrous MgSO4, filtered and concentrated to a yellow oil. The crude material was treated with hexanes and adsorbed onto silica gel and passed through a Redi-Sep® pre-packed silica gel column (80 g) eluting with 0-20% EtOAc/hexane. The product-containing fractions were concentrated to afford (R)-3-(tert-butyldimethylsilyloxy)-1-(2-nitro-4-(trifluoromethyl)phenyl)piperidine as a yellow oil. MS m/z=405 [M+H]+. Calc'd for C18H27F3N2O3Si: 404.

Workup

  1. additionwas added
  2. washThe organic layer was washed 2× H2O, 1× brine
  3. dry with materialdried over anhydrous MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated to a yellow oil
  6. additionThe crude material was treated with hexanes
  7. washeluting with 0-20% EtOAc/hexane
  8. concentrationThe product-containing fractions were concentrated

Sources & evidence

ORD record
ord-98d8e800aa58476da2509232a48abcc8
Source dataset
uspto-grants-2013_10
Patent number
US08557996B2

Reaction notes

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