Ethyl orthoformate → 4-ethoxy-3-fluoroanilino-N-(2,4-dichloro-5-methoxyphenyl)-2-cyano-2-propenamide

HRID 1593771

Reaction equation

HRID 1593771 reaction equation
[C:1]([CH2:3][C:4]([NH:6][C:7]1[CH:12]=[C:11]([O:13][CH3:14])[C:10]([Cl:15])=[CH:9][C:8]=1[Cl:16])=[O:5])#[N:2].[CH2:17]([O:19][C:20]1[CH:26]=[CH:25][C:23]([NH2:24])=[CH:22][C:21]=1[F:27])[CH3:18].[CH2:28](OC(OCC)OCC)C>C(O)(C)C>[CH2:17]([O:19][C:20]1[CH:26]=[CH:25][C:23]([NH:24][CH:28]=[C:3]([C:1]#[N:2])[C:4]([NH:6][C:7]2[CH:12]=[C:11]([O:13][CH3:14])[C:10]([Cl:15])=[CH:9][C:8]=2[Cl:16])=[O:5])=[CH:22][C:21]=1[F:27])[CH3:18]

Participants

5

Reactant 3

HCID 31214Ethyl orthoformate2×HCID 160991782-cyano-N-(2,4-dichloro-5-methoxyphenyl)acetamideHCID 195992054-Ethoxy-3-fluoroaniline

Product 1

HCID 693122634-ethoxy-3-fluoroanilino-N-(2,4-dichloro-5-methoxyphenyl)-2-cyano-2-propenamideYield 67%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

To a suspension of 2-cyano-N-(2,4-dichloro-5-methoxyphenyl)acetamide (5.9 g, 22.7 mmol) in 400 mL of isopropanol was added 4-ethoxy-3-fluoroaniline (3.7 g, 23.8 mmol). This mixture was heated to reflux to give a clear solution. To this solution, triethylorthoformate (11.6 mL, 69.6 mmol) was added dropwise and the reaction mixture was heated at reflux for 18 hours. Additional triethylorthoformate (11.6 mL, 69.6 mmol) was added dropwise and the reaction mixture was heated at reflux for 42 hours. The mixture was allowed to cool to room temperature and the solid was collected by filtration, washed with ethyl acetate, and dried in vacuo at 40° C. to give 6.4 g (67%) of 4-ethoxy-3-fluoroanilino-N-(2,4-dichloro-5-methoxyphenyl)-2-cyano-2-propenamide as a grey solid, mp 245-247° C.; MS 424.1, 426.1 (M+H)+

Workup

  1. temperatureThis mixture was heated
  2. temperatureto reflux
  3. customto give a clear solution
  4. temperaturethe reaction mixture was heated
  5. temperatureat reflux for 18 hours
  6. temperaturethe reaction mixture was heated
  7. temperatureat reflux for 42 hours
  8. filtrationthe solid was collected by filtration
  9. washwashed with ethyl acetate
  10. customdried in vacuo at 40° C.

Sources & evidence

ORD record
ord-1411a352eaa849ae8ced2bb3a73ce921
Source dataset
uspto-grants-2007_11
Patent number
US07297795B2

Linked notes

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