Trifluoroacetic anhydride → Tert-butyl 2-cyano-4,4-difluoropiperidine-1-carboxylate

HRID 526926Notes

Reaction equation

HRID 526926 reaction equation
[C:1]([CH:4]1[CH2:9][C:8]([F:11])([F:10])[CH2:7][CH2:6][N:5]1[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])(=O)[NH2:2].FC(F)(F)C(OC(=O)C(F)(F)F)=O>C(Cl)Cl.C([O-])(O)=O.[Na+]>[C:1]([CH:4]1[CH2:9][C:8]([F:11])([F:10])[CH2:7][CH2:6][N:5]1[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])#[N:2]

Participants

5

Reactant 2

HCID 9845Trifluoroacetic anhydrideHCID 67286514Tert-butyl 2-carbamoyl-4,4-difluoropiperidine-1-carboxylate2×

Product 1

HCID 67284864Tert-butyl 2-cyano-4,4-difluoropiperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of tert-butyl 2-carbamoyl-4,4-difluoro-piperidine-1-carboxylate, 13g, (1.72 g, 6.51 mmol) in CH2Cl2 (50 mL) was added was N,N-triethylamine (2.03 mL, 14.61 mmol) followed by the dropwise addition of (2,2,2-trifluoroacetyl)-2,2,2-trifluoroacetate (1.02 mL, 7.32 mmol). After 15 minutes, the mixture was diluted with aqueous saturated NaHCO3 solution and the layers were separated. The organic phase was washed with water, dried over Na2SO4, filtered and evaporated to dryness. The crude residue was passed through a plug of silica gel and eluted with 10-30% EtOAc/hexanes to afford the desired product, 13h.

Workup

  1. customthe layers were separated
  2. washThe organic phase was washed with water
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. customevaporated to dryness
  6. washeluted with 10-30% EtOAc/hexanes

Sources & evidence

ORD record
ord-ceb5fbefd49c41c19d987aa9b349c68a
Source dataset
uspto-grants-2016_05
Patent number
US09345708B2

Reaction notes

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