Acetic Acid → Ethyl 1-(3,3,3-trifluoropropyl)piperidine-4-carboxylate

HRID 1927017Notes

Reaction equation

HRID 1927017 reaction equation
[NH:1]1[CH2:11][CH2:10][CH:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH2:3][CH2:2]1.[F:12][C:13]([F:18])([F:17])[CH2:14][CH:15]=O.CC(O)=O.C([BH3-])#N.[Na+]>C1COCC1.CO>[F:12][C:13]([F:18])([F:17])[CH2:14][CH2:15][N:1]1[CH2:2][CH2:3][CH:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH2:10][CH2:11]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 680283,3,3-TrifluoropropanalHCID 70770Ethyl 4-piperidinecarboxylateHCID 5003444Sodium cyanoborohydride

Product 1

HCID 59334005Ethyl 1-(3,3,3-trifluoropropyl)piperidine-4-carboxylateYield 68.2%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl isonipecotate (3.00 g, 19.1 mmol) in THF (20 mL) and MeOH (20 mL) was added 3,3,3-trifluoropropionaldehyde (2.14 g, 19.1 mmol) and AcOH (1.09 mL, 19.1 mmol) followed by sodium cyanoborohydride (1.20 g, 19.1 mmol). The reaction was allowed to stir for 10 min., at which time the reaction was quenched with water (15 mL) then made basic with NaHCO3 and extracted with EtOAc. The organic layer was washed with brine, dried and concentrated in vacuo to yield a white powder (3.3 g, 68%). Mass Spectrum: Calcd for C11H19NF3O2 (M+H): 254. Found: 254.

Workup

  1. customwas quenched with water (15 mL)
  2. extractionextracted with EtOAc
  3. washThe organic layer was washed with brine
  4. customdried
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8a6d0f51a97f412aa99fb9112b6bfbc3
Source dataset
uspto-grants-2012_05
Patent number
US08183255B2

Reaction notes

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