Imidazole → tert-Butyl 4-{[tert-butyl(dimethyl)silyl]oxy}-6-cyano-spiro[chroman-2,4'-piperidine]-1'-carboxylate

HRID 1096922Notes

Reaction equation

HRID 1096922 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]2[C:22](=[CH:23][CH:24]=1)[O:21][C:8]1([CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]1)[CH2:7][CH:6]2[OH:25])#[N:2].N1C=CN=C1.[CH3:31][C:32]([Si:35](Cl)([CH3:37])[CH3:36])([CH3:34])[CH3:33]>CN(C=O)C>[Si:35]([O:25][CH:6]1[C:5]2[C:22](=[CH:23][CH:24]=[C:3]([C:1]#[N:2])[CH:4]=2)[O:21][C:8]2([CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)[CH2:7]1)([C:32]([CH3:34])([CH3:33])[CH3:31])([CH3:37])[CH3:36]

Participants

5

Reactant 3

HCID 795Imidazole2×HCID 28928tert-Butyldimethylsilyl chloride2×HCID 66649142tert-Butyl 6-cyano-4-hydroxy-spiro[chroman-2,4'-piperidine]-1'-carboxylate

Product 1

HCID 66649537tert-Butyl 4-{[tert-butyl(dimethyl)silyl]oxy}-6-cyano-spiro[chroman-2,4'-piperidine]-1'-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 15.1 g of tert-butyl 6-cyano-4-hydroxy-spiro[chroman-2,4′-piperidine]-1′-carboxylate in DMF were added 3.6 g of imidazole and 7.95 g of TBSCl at rt, and the reaction mixture was stirred at rt for 1d. To this reaction mixture was added 598 mg of imidazole and 1.3 g of TBSCl at rt, and the reaction mixture was stirred at rt for 1d. The reaction mixture was poured into ice-cold brine, and the aqueous mixture was extracted with AcOEt twice. The combined organic layers were washed with H2O and brine, dried over Na2SO4, filtered, and concentrated in reduced pressure. The residue was purified by column chromatography on silica gel using a mixture of hexane and AcOEt (100/0-80/20) as eluent to give the intended compound.

Workup

  1. additionThe reaction mixture was poured into ice-cold brine
  2. extractionthe aqueous mixture was extracted with AcOEt twice
  3. washThe combined organic layers were washed with H2O and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in reduced pressure
  7. customThe residue was purified by column chromatography on silica gel using
  8. additiona mixture of hexane and AcOEt (100/0-80/20) as eluent
  9. customto give the intended compound

Sources & evidence

ORD record
ord-6a6b934481a148a689f900a3a66777d5
Source dataset
uspto-grants-2012_03
Patent number
US08138197B2

Reaction notes

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