Ethyl cyanoacetate → Ethyl 2-cyano-3-oxo-3-(2-{[3-(trifluoromethyl)phenyl]amino}-3-pyridinyl)propanoate

HRID 2183779Notes

Reaction equation

HRID 2183779 reaction equation
[H-].[Na+].[C:3]([CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7])#[N:4].[F:11][C:12]([F:39])([F:38])[C:13]1[CH:14]=[C:15]([NH:19][C:20]2[N:37]=[CH:36][CH:35]=[CH:34][C:21]=2[C:22](OC2C=CC([N+]([O-])=O)=CC=2)=[O:23])[CH:16]=[CH:17][CH:18]=1>C1(C)C=CC=CC=1>[C:3]([CH:5]([C:22](=[O:23])[C:21]1[C:20]([NH:19][C:15]2[CH:16]=[CH:17][CH:18]=[C:13]([C:12]([F:39])([F:11])[F:38])[CH:14]=2)=[N:37][CH:36]=[CH:35][CH:34]=1)[C:6]([O:8][CH2:9][CH3:10])=[O:7])#[N:4]

Participants

5

Reactant 3

HCID 7764Ethyl cyanoacetateHCID 24758Sodium hydrideHCID 219481574-Nitrophenyl 2-{[3-(trifluoromethyl)phenyl]amino}nicotinate

Product 1

HCID 21948193Ethyl 2-cyano-3-oxo-3-(2-{[3-(trifluoromethyl)phenyl]amino}-3-pyridinyl)propanoate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a stirred mixture of NaH (524 mg, 21.8 mmol) in toluene (20 mL) was added dropwise ethyl cyanoacetate (3.7 g, 32.7 mmol, 3.5 mL). The slurry was stirred for 1 h and then 4-nitrophenyl 2-{[3-(trifluoromethyl)phenyl]amino}nicotinate (4.4 g, 10.9 mmol) was added. The reaction mixture was stirred for 1 h and then quenched with water (20 mL). CH2Cl2 (30 mL) was added and the layers were partitioned. The organic layer was washed with brine (2×) and dried over Na2SO4. The solvent was removed in vacuo and the residue was purified by silica gel flash chromatography (5:1 to 2:1 Hex:EtOAc) to afford 3 Ethyl 2-cyano-3-oxo-3-(2-{[3-(trifluoromethyl)phenyl]amino}-3-pyridinyl)propanoate. (6 g, 87%): LCMS RT: 2.83 min, MH+: 378.0.

Workup

  1. stirringThe reaction mixture was stirred for 1 h
  2. customquenched with water (20 mL)
  3. additionCH2Cl2 (30 mL) was added
  4. customthe layers were partitioned
  5. washThe organic layer was washed with brine (2×)
  6. dry with materialdried over Na2SO4
  7. customThe solvent was removed in vacuo
  8. customthe residue was purified by silica gel flash chromatography (5:1 to 2:1 Hex:EtOAc)

Sources & evidence

ORD record
ord-b2dd20e05c8341fab2a7c5d3e397d4e4
Source dataset
uspto-grants-2005_05
Patent number
US06900205B2

Reaction notes

Loading…