2-(Trifluoromethyl)aniline → N-(2-trifluoromethyl-phenyl)-malonamic acid benzyl ester

HRID 641598Notes

Reaction equation

HRID 641598 reaction equation
[C:1]([O:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)(=[O:6])[CH2:2][C:3]([O-:5])=O.C(N(CC)C(C)C)(C)C.[F:24][C:25]([F:34])([F:33])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[NH2:32].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl.CN(C=O)C>[CH2:8]([O:7][C:1](=[O:6])[CH2:2][C:3]([NH:32][C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=1[C:25]([F:24])([F:33])[F:34])=[O:5])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

6

Reactant 4

HCID 69222-(Trifluoromethyl)anilineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 22247814Benzyl malonate

Product 1

HCID 68616692N-(2-trifluoromethyl-phenyl)-malonamic acid benzyl esterYield 57.6%

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

A solution of mono-benzyl malonate (890 mg, 4.6 mmol) in 3:1 CH2Cl2/DMF (24 mL) was treated sequentially with N,N-diisopropylethylamine (2.0 mL, 11.5 mmol), 2-trifluoromethyl-phenylamine (0.6 mL, 4.6 mmol), and HATU (2.1 g, 5.5 mmol). The mixture was stirred for 12 h at RT, concentrated in vacuo, and partitioned between EtOAc and sat. NH4Cl. The aqueous phase was extracted with EtOAc (1×). The combined organic extracts were washed with sat. NaHCO3 and brine, dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by flash chromatography to provide N-(2-trifluoromethyl-phenyl)-malonamic acid benzyl ester as an oil (894 mg, 57% yield). This material was dissolved in EtOAc (35 mL). The resultant solution was charged with 10% Pd/C (178 mg), stirred under H2 (1 atm) for 12 h at RT, filtered, and concentrated in vacuo to provide N-(2-trifluoromethyl-phenyl)-malonamic acid (621 mg, 95% yield). MS found: (M+H)+=248.02.

Workup

  1. concentrationconcentrated in vacuo
  2. custompartitioned between EtOAc and sat. NH4Cl
  3. extractionThe aqueous phase was extracted with EtOAc (1×)
  4. washThe combined organic extracts were washed with sat. NaHCO3 and brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-51d288cbda5b421386b6491c109756ce
Source dataset
uspto-grants-2010_04
Patent number
US07696205B2

Reaction notes

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