Tetrabutylammonium Fluoride → Tert-butyl 3-hydroxy-3-(trifluoromethyl)piperidine-1-carboxylate

HRID 69910Notes

Reaction equation

HRID 69910 reaction equation
CCCC[N+](CCCC)(CCCC)CCCC.[F-].[F:19][C:20]([F:40])([F:39])[C:21]1([O:34][Si](C)(C)C)[CH2:26][CH2:25][CH2:24][N:23]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:22]1>C1COCC1>[OH:34][C:21]1([C:20]([F:40])([F:19])[F:39])[CH2:26][CH2:25][CH2:24][N:23]([C:27]([O:29][C:30]([CH3:33])([CH3:31])[CH3:32])=[O:28])[CH2:22]1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 69045134Tert-butyl 3-(trifluoromethyl)-3-(trimethylsilyloxy)piperidine-1-carboxylate

Product 1

HCID 50986438Tert-butyl 3-hydroxy-3-(trifluoromethyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A 1.0 M solution of TBAF in THF (1 eq) was added to a solution of tert-butyl 3-(trifluoromethyl)-3-(trimethylsilyloxy)piperidine-1-carboxylate (1 eq) in THF (0.2 M). After stirring for 16 h at rt the reaction mixture was concentrated in vacuo. The resulting residue was dissolved in EtOAc, washed with brine, then dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The crude residue was dissolved in CH2Cl2, loaded onto a SiO2 column, and purified by flash chromatography to give tert-butyl 3-hydroxy-3-(trifluoromethyl)piperidine-1-carboxylate. 19F NMR (282 MHz, CDCl3): δ−83.74 ppm; 1H NMR (300 MHz, CDCl3): δ 4.04-4.16 (m, 2H), 2.72-3.01 (m, 2H), 1.50-2.04 (m, 4H), 1.47 (s, 9H).

Workup

  1. concentrationwas concentrated in vacuo
  2. dissolutionThe resulting residue was dissolved in EtOAc
  3. washwashed with brine
  4. dry with materialdried over anhydrous MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. dissolutionThe crude residue was dissolved in CH2Cl2
  8. custompurified by flash chromatography

Sources & evidence

ORD record
ord-5e47a960cc864c7f9c10739419317227
Source dataset
uspto-grants-2014_09
Patent number
US08822497B2

Reaction notes

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