Iodine → N-(3-trifluoromethoxy-phenyl)-malonamic acid benzyl ester

HRID 2225206Notes

Reaction equation

HRID 2225206 reaction equation
II.[C:3]([O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)(=[O:8])[CH2:4][C:5]([O-:7])=O.C(N(CC)C(C)C)(C)C.[F:26][C:27]([F:37])([F:36])[O:28][C:29]1[CH:30]=[C:31]([NH2:35])[CH:32]=[CH:33][CH:34]=1.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>[CH2:10]([O:9][C:3](=[O:8])[CH2:4][C:5]([NH:35][C:31]1[CH:32]=[CH:33][CH:34]=[C:29]([O:28][C:27]([F:26])([F:36])[F:37])[CH:30]=1)=[O:7])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

7

Reactant 5

HCID 807IodineHCID 737533-(Trifluoromethoxy)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 69284656N-(3-trifluoromethoxy-phenyl)-malonamic acid benzyl esterYield 83.4%

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

Preparation I2, Step 1: A solution of mono-benzyl malonate (1.1 g, 5.6 mmol) in 3:1 CH2Cl2/DMF (28 mL) was treated sequentially with N,N-diisopropylethylamine (2.5 mL, 14.0 mmol), meta-trifluoromethoxy-phenylamine (0.75 mL, 5.6 mmol), and HATU (2.6 g, 6.7 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-(3-trifluoromethoxy-phenyl)-malonamic acid benzyl ester as an oil (1.65 g).

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-cf5ec41b3c0c4d58ae8cb32e6109bb1c
Source dataset
uspto-grants-2008_05
Patent number
US07378409B2

Reaction notes

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