Methyl iodide → 4-[Methyl-(2-trifluoromethyl-phenyl)-amino]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1093549Notes

Reaction equation

HRID 1093549 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[C:21]([F:24])([F:23])[F:22])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:27]I>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]([CH3:27])[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[C:21]([F:24])([F:22])[F:23])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 66591750tert-Butyl 4-((2-(trifluoromethyl)phenyl)amino)piperidine-1-carboxylate

Product 1

HCID 665915074-[Methyl-(2-trifluoromethyl-phenyl)-amino]-piperidine-1-carboxylic acid tert-butyl esterYield 263.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-(2-trifluoromethyl-phenylamino)-piperidine-1-carboxylic acid tert-butyl ester (0.5 g, 0.00053 mole), in DMF (5 mL) was added, NaH (60% w/w dispersion in oil) (0.0696 g, 0.0029 mole) and the resulting mixture was stirred at ambient temperature for 10 minutes under an atmosphere of nitrogen. Methyl iodide (0.617 g, 0.00435 mole) was then added, and stirring was continued for 30 minutes at ambient temperature. The reaction mixture was quenched with aqueous 10% NH4Cl solution and the product was extracted with ether. The organic layer was washed with aqueous NaHCO3 solution followed by brine solution. The ether layer was then collected, dried over sodium sulfate and concentrated under reduced pressure to afford 0.5 g of 4-[methyl-(2-trifluoromethyl-phenyl)-amino]-piperidine-1-carboxylic acid tert-butyl ester that which was used in the next step without further purification. 4-[Methyl-(2-trifluoromethyl-phenyl)-amino]-piperidine-1-carboxylic acid tert-butyl ester obtained (0.5 g) was stirred in dioxane.HCl (5 mL) for 30 minutes. The reaction mixture was concentrated under reduced pressure to afford 0.36 g (88%) of methyl-piperidin-4-yl-(2-trifluoromethyl-phenyl)-amine hydrochloride which was used in the next step without further purification.

Workup

  1. customThe reaction mixture was quenched with aqueous 10% NH4Cl solution
  2. extractionthe product was extracted with ether
  3. washThe organic layer was washed with aqueous NaHCO3 solution
  4. customThe ether layer was then collected
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-7e31c76745fe4fd3a81f764b1cff196b
Source dataset
uspto-grants-2012_03
Patent number
US08129376B2

Reaction notes

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