Methanol → (E)-ethyl 3-(4-acetamido-3-(2-methoxyethoxy)phenylamino)-2-cyanoacrylate

HRID 403652Notes

Reaction equation

HRID 403652 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[C:10]([N+:12]([O-])=O)[CH:9]=[CH:8][C:7]=1[NH:15][C:16](=[O:18])[CH3:17].CO.[H][H].[C:23](/[C:25](=[CH:31]\OCC)/[C:26]([O:28][CH2:29][CH3:30])=[O:27])#[N:24]>[Pd].C1COCC1.C1(C)C=CC=CC=1.C(O)(=O)C>[C:16]([NH:15][C:7]1[CH:8]=[CH:9][C:10]([NH:12]/[CH:31]=[C:25](\[C:23]#[N:24])/[C:26]([O:28][CH2:29][CH3:30])=[O:27])=[CH:11][C:6]=1[O:5][CH2:4][CH2:3][O:2][CH3:1])(=[O:18])[CH3:17]

Participants

9

Reactant 4

HCID 887MethanolHCID 1715183Ethyl 2-cyano-3-ethoxyacrylateHCID 67287383N-(2-(2-methoxyethoxy)-4-nitrophenyl)acetamideHCID 178418361HCID 178418361, compound

Product 1

HCID 67474100(E)-ethyl 3-(4-acetamido-3-(2-methoxyethoxy)phenylamino)-2-cyanoacrylateYield 75.1%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 176Acetic AcidSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To N-(2-(2-methoxyethoxy)-4-nitrophenyl)acetamide (75 g, 0.295 mol, 1.00 equiv) was added methanol (600 ml), 10% Pd/C (6 g), and glacial acetic acid (60 ml) in a vessel which subject to a closed pressure vessel. Replacement of Kettle access from air to 5 atm hydrogen at room temperature was deployed and reacted for 5 hours. The reaction mixture was filtered, and concentrated. Toluene (440 ml), THF (220 ml), and (E)-ethyl 2-cyano-3-ethoxyacrylate (76 g, 0.497 mol, 1.68 equiv) were added and then refluxed for 16 h. The reaction mixture was cooled to room temperature, filtered, washed and dried with tetrahydrofuran to give 77 g product as off-white solid. MS (ESI) m/z: 347 (M+1).

Workup

  1. customsubject to a closed pressure vessel
  2. customat room temperature
  3. customreacted for 5 hours
  4. filtrationThe reaction mixture was filtered
  5. concentrationconcentrated
  6. temperaturerefluxed for 16 h
  7. filtrationfiltered
  8. washwashed
  9. dry with materialdried with tetrahydrofuran

Sources & evidence

ORD record
ord-c3276314a347489790600ba719f9412d
Source dataset
uspto-grants-2014_06
Patent number
US08748453B2

Reaction notes

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