2-(Trifluoromethyl)aniline → tert-Butyl 4-((2-(trifluoromethyl)phenyl)amino)piperidine-1-carboxylate

HRID 552128Notes

Reaction equation

HRID 552128 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]([F:11])([F:10])[F:9].[C:12]([N:19]1[CH2:24][CH2:23][C:22](=O)[CH2:21][CH2:20]1)([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13].C([BH3-])#N.[Na+].[OH-].[Na+]>C1COCC1.C(OCC)(=O)C.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[C:15]([O:14][C:12]([N:19]1[CH2:24][CH2:23][CH:22]([NH:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=2[C:8]([F:9])([F:10])[F:11])[CH2:21][CH2:20]1)=[O:13])([CH3:18])([CH3:16])[CH3:17]

Participants

8

Reactant 4

HCID 69222-(Trifluoromethyl)anilineHCID 14798Sodium HydroxideHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5003444Sodium cyanoborohydride

Product 1

HCID 66591750tert-Butyl 4-((2-(trifluoromethyl)phenyl)amino)piperidine-1-carboxylateYield 95.2%

Reagents, catalysts & solvents 3

HCID 11026Titanium isopropoxideCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Titanium isopropoxide (2.5 mL, 8.46 mmol) was added to a solution of 2-aminobenzotrifluoride (0.6 mL, 4.82 mmol) and 1-Boc-4-piperidone (1.05 g, 5.26 mmol)) in THF (3 mL), the resulting mixture was stirred at ambient temperature for 4 hours, then sodium cyanoborohydride (0.800 g, 12.73 mmol) was added. The stirring was continued overnight. Aqueous sodium hydroxide (2.0 mL, 1.0 M) was added and the mixture was stirred for another 15 minutes. The reaction mixture was diluted with ethyl acetate (250 mL), washed with water, and brine, dried over anhydrous Na2SO4, and concentrated. The residue was purified by flash chromatography to afford 4-(2-trifluoromethylphenylamino)piperidine-1-carboxylic acid tert-butyl ester (1.58 g, 95%). MS (ES+) m/z 345.1 (M+1).

Workup

  1. waitThe stirring was continued overnight
  2. stirringthe mixture was stirred for another 15 minutes
  3. washwashed with water, and brine
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-7209266d3441434db6eb2158da4c08e3
Source dataset
uspto-grants-2011_05
Patent number
US07951805B2

Reaction notes

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