2,2,6,6-Tetramethylpiperidine → HCID 59826893, compound

HRID 1426691Notes

Reaction equation

HRID 1426691 reaction equation
CC1(C)CCCC(C)(C)N1.C([Li])CCC.[F:16][C:17]([F:25])([F:24])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][N:19]=1.[F:26][C:27]1([F:41])[C:31](=[CH2:32])[CH2:30][N:29]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[C:28]1=[O:40].[Cl-].[NH4+]>O1CCCC1.CCCCCC>[F:26][C:27]([F:41])([C:28](=[O:40])[C:23]1[C:18]([C:17]([F:25])([F:24])[F:16])=[N:19][CH:20]=[CH:21][CH:22]=1)[C:31](=[CH2:32])[CH2:30][NH:29][C:33](=[O:34])[O:35][C:36]([CH3:37])([CH3:38])[CH3:39]

Participants

8

Reactant 5

HCID 130352,2,6,6-TetramethylpiperidineHCID 25517Ammonium ChlorideHCID 136199TrifluoromethylpyridineHCID 598268761055306-64-3HCID 178418339Butyllithium

Product 1

HCID 59826893HCID 59826893, compoundYield 87%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolvent

Procedure

Under a nitrogen atmosphere, to a solution of 2,2,6,6-tetramethylpiperidine (10.2 g) in anhydrous tetrahydrofuran (100 mL) was added dropwise a 1.61 mol/L hexane solution (40.5 mL) of n-butyllithium at −78° C., and the mixture was stirred at the same temperature for 15 min. To the obtained solution was added dropwise a solution of 2-(trifluoromethyl)pyridine (10.2 g) in anhydrous tetrahydrofuran (10 mL) at the same temperature over 30 min, and the mixture was stirred for 2 hr. A solution of tert-butyl 3,3-difluoro-4-methylene-2-oxopyrrolidine-1-carboxylate (7.65 g) in anhydrous tetrahydrofuran (10 mL) solution was added dropwise to the obtained suspension at the same temperature, and the mixture was stirred for 2 hr. Saturated aqueous ammonium chloride solution was added, and the mixture was extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate solution, water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane:ethyl acetate=3:1) to give the title compound as a yellow oil (yield 10.8 g, 87%).

Workup

  1. stirringthe mixture was stirred for 2 hr
  2. stirringthe mixture was stirred for 2 hr
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe extract was washed successively with saturated aqueous sodium hydrogen carbonate solution, water and saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (eluent: hexane:ethyl acetate=3:1)

Sources & evidence

ORD record
ord-ab7e26420a62417ab53984f33f5cd995
Source dataset
uspto-grants-2015_01
Patent number
US08933105B2

Reaction notes

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