Trifluoroacetic acid → Ethyl 3-amino-2,2-difluoropropanoate

HRID 220717Notes

Reaction equation

HRID 220717 reaction equation
C([N:8](CC1C=CC=CC=1)[CH2:9][C:10]([F:17])([F:16])[C:11]([O:13][CH2:14][CH3:15])=[O:12])C1C=CC=CC=1.C(O)(C(F)(F)F)=O>CCO>[NH2:8][CH2:9][C:10]([F:17])([F:16])[C:11]([O:13][CH2:14][CH3:15])=[O:12]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 11256065Ethyl 3-(dibenzylamino)-2,2-difluoropropanoate

Product 1

HCID 49853528Ethyl 3-amino-2,2-difluoropropanoateYield 94%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

In a round bottom flask, ethyl 3-(dibenzylamino)-2,2-difluoropropanoate (1.72 g, 5.2 mmol) was solubilized in EtOH (25 mL) and TFA added (0.4 mL, 5.5 mmol). Under an atmosphere of nitrogen Pd(OH)2/C (170 mg of 20% Pd by wt. wet) was added. The reaction mixture was repeatedly purged with nitrogen and then left under hydrogen overnight. At this point the reaction was deemed complete by LCMS, filtered through a pad of Celite, the pad washed with EtOH and the filtrate concentrated without heating to yield ethyl 3-amino-2,2-difluoropropanoate, as its TFA salt, as a foggy syrup which starts to crystallize upon standing (1.31 g, 94% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.29 (t, J=7.20 Hz, 3 H) 3.72 (t, J=16.17 Hz, 2 H) 4.34 (q, J=7.24 Hz, 2 H). [M+H] calc'd for C5H9F2NO2, 154; found 154.

Workup

  1. additionUnder an atmosphere of nitrogen Pd(OH)2/C (170 mg of 20% Pd by wt. wet) was added
  2. customThe reaction mixture was repeatedly purged with nitrogen
  3. filtrationfiltered through a pad of Celite
  4. washthe pad washed with EtOH
  5. concentrationthe filtrate concentrated
  6. temperaturewithout heating

Sources & evidence

ORD record
ord-0e2ecdabcd3e4165bcdaf31769bce0de
Source dataset
uspto-grants-2012_06
Patent number
US08202990B2

Reaction notes

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