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

HRID 1593770Notes

Reaction equation

HRID 1593770 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].[NH2:17][C:18]1[CH:19]=[CH:20][C:21]([Br:26])=[C:22]([O:24][CH3:25])[CH:23]=1.[CH2:27](OC(OCC)OCC)C>C(O)(C)C>[Br:26][C:21]1[CH:20]=[CH:19][C:18]([NH:17][CH:27]=[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:23][C:22]=1[O:24][CH3:25]

Participants

5

Reactant 3

HCID 31214Ethyl orthoformate2×HCID 70182544-Bromo-3-methoxyanilineHCID 160991782-cyano-N-(2,4-dichloro-5-methoxyphenyl)acetamide

Product 1

HCID 693122584-bromo-3-methoxyanilino-N-(2,4-dichloro-5-methoxyphenyl)-2-cyano-2-propenamideYield 73.2%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

To a suspension of 2-cyano-N-(2,4-dichloro-5-methoxyphenyl)acetamide (6.1 g, 23.5 mmol) in 500 mL of isopropanol was added 5-amino-2-bromoanisole (5.0 g, 24.8 mmol). This mixture was heated to reflux to give a clear yellow solution. To this solution, triethylorthoformate (10.6 mL, 63.5 mmol) was added dropwise and the reaction mixture was heated at reflux for 5 hours. An additional 10.6 mL of triethylorthoformate was added and the mixture was heated at reflux overnight. The mixture was allowed to cool to room temperature. The solid was collected by filtration, washed with isopropanol and ethyl acetate, and then dried overnight at ˜40° C. under reduced pressure to give 8.1 g (73%) of 4-bromo-3-methoxyanilino-N-(2,4-dichloro-5-methoxyphenyl)-2-cyano-2-propenamide as a yellow solid, mp >250° C.; MS (ES) m/z470.0, 472.0 (M+H)+

Workup

  1. temperatureThis mixture was heated
  2. temperatureto reflux
  3. customto give a clear yellow solution
  4. temperaturethe reaction mixture was heated
  5. temperatureat reflux for 5 hours
  6. temperaturethe mixture was heated
  7. temperatureat reflux overnight
  8. filtrationThe solid was collected by filtration
  9. washwashed with isopropanol and ethyl acetate
  10. customdried overnight at ˜40° C. under reduced pressure

Sources & evidence

ORD record
ord-2a5b7e23e3524c69bccccc1f329c4660
Source dataset
uspto-grants-2007_11
Patent number
US07297795B2

Reaction notes

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