Trifluoroacetic acid → Piperidine-4-carboxylic acid (4-isopropyl-phenyl)-amide

HRID 2381164Notes

Reaction equation

HRID 2381164 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([C:14](=[O:25])[NH:15][C:16]2[CH:21]=[CH:20][C:19]([CH:22]([CH3:24])[CH3:23])=[CH:18][CH:17]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl>[CH:22]([C:19]1[CH:18]=[CH:17][C:16]([NH:15][C:14]([CH:11]2[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]2)=[O:25])=[CH:21][CH:20]=1)([CH3:24])[CH3:23]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acid2×HCID 292052294-(4-Isopropyl-phenylcarbamoyl)-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 18071890Piperidine-4-carboxylic acid (4-isopropyl-phenyl)-amideYield 83.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-(4-Isopropyl-phenylcarbamoyl)-piperidine-1-carboxylic acid tert-butyl ester (1.68 g) was dissolved in methylene chloride (50 ml), trifluoroacetic acid (2.75 g) was added at 0° C. and under an argon atmosphere and the mixture was stirred for 12 h at RT. Further trifluoroacetic acid (1.1 g) was added and stirring was continued for 1.5 h to complete the reaction. The reaction mixture was partitioned between methylene chloride and aqueous 1M NaOH, the layers were separated and the aqueous layer washed with 2M aqueous KHCO3 then dried over Na2SO4. The solvent was evaporated off, the residue was triturated with diethyl ether/heptane to give the desired piperidine-4-carboxylic acid (4-isopropyl-phenyl)-amide (1 g) as a white solid that was directly used in the next step.

Workup

  1. stirringstirring
  2. waitwas continued for 1.5 h
  3. customthe reaction
  4. customThe reaction mixture was partitioned between methylene chloride and aqueous 1M NaOH
  5. customthe layers were separated
  6. washthe aqueous layer washed with 2M aqueous KHCO3
  7. dry with materialthen dried over Na2SO4
  8. customThe solvent was evaporated off
  9. customthe residue was triturated with diethyl ether/heptane

Sources & evidence

ORD record
ord-1caf7480eeb94f788b3ee9ab19206942
Source dataset
uspto-grants-2012_09
Patent number
US08258158B2

Reaction notes

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