Pyridine → N-[2-Methyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-butyramide

HRID 602517Notes

Reaction equation

HRID 602517 reaction equation
C(OC(=O)[N:7]([C:19]1[CH:24]=[CH:23][C:22]([NH2:25])=[C:21]([CH3:26])[CH:20]=1)[CH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][CH:10]=1)(C)(C)C.N1C=CC=CC=1.[C:34](Cl)(=[O:38])[CH2:35][CH2:36][CH3:37]>O1CCCC1.C(OCC)(=O)C>[CH3:26][C:21]1[CH:20]=[C:19]([NH:7][CH2:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]([F:16])([F:17])[F:18])=[CH:11][CH:10]=2)[CH:24]=[CH:23][C:22]=1[NH:25][C:34](=[O:38])[CH2:35][CH2:36][CH3:37]

Participants

6

Reactant 3

HCID 1049PyridineHCID 8855Butyryl chlorideHCID 67266881(4-Amino-3-methylphenyl)-(4-trifluoromethylbenzyl)-carbamic acid tert-butyl ester

Product 1

HCID 67266732N-[2-Methyl-4-(4-trifluoromethyl-benzylamino)-phenyl]-butyramideYield 49.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (4-amino-3-methylphenyl)-(4-trifluoromethyl-benzyl)-carbamic acid tert-butyl ester (500 mg, 1.31 mmol) in dry tetrahydrofuran (10 mL) at 0° C. was added pyridine (159 mL, 1.97 mmol) followed by butyryl chloride (164 μL, 1.58 mmol) dropwise. After 5 minutes, the reaction mixture was allowed to warm to room temperature, and stirring was continued for 1 hour. The reaction mixture was then diluted with ethyl acetate, washed with 2 N HCl, saturated aqueous sodium bicarbonate twice, and brine, and was then dried over magnesium sulfate. Solvents were evaporated in vacuo and the residue was dissolved in a 1:1 mixture of dichloromethane and trifluoroacetic acid. After 30 minutes at room temperature the mixture was evaporated to dryness, the residue was dissolved in ethyl acetate (10 mL), the solution was washed twice with saturated aqueous sodium bicarbonate, twice with water, and was then dried over sodium sulfate. Evaporation of the solvents and recrystallization of the residue from ethyl acetate:heptane gave the title compound as a colorless solid (226 mg, 49%).

Workup

  1. waitwas continued for 1 hour
  2. washwashed with 2 N HCl, saturated aqueous sodium bicarbonate twice
  3. dry with materialbrine, and was then dried over magnesium sulfate
  4. customSolvents were evaporated in vacuo
  5. dissolutionthe residue was dissolved in a 1:1 mixture of dichloromethane and trifluoroacetic acid
  6. customAfter 30 minutes at room temperature the mixture was evaporated to dryness
  7. dissolutionthe residue was dissolved in ethyl acetate (10 mL)
  8. washthe solution was washed twice with saturated aqueous sodium bicarbonate, twice with water
  9. dry with materialwas then dried over sodium sulfate
  10. customEvaporation of the solvents and recrystallization of the residue from ethyl acetate

Sources & evidence

ORD record
ord-915b18889b414430b5592ea460fad3e9
Source dataset
uspto-grants-2011_03
Patent number
US07906537B2

Reaction notes

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