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

HRID 74902

Reaction equation

HRID 74902 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-carboxylate

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-c409c9554e0042f3a22511bb23544bf9
Source dataset
uspto-grants-2014_09
Patent number
US08829007B2

Linked notes

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