Hydrochloric Acid → Ethyl[(Z)-2-cyano-1-(2,4-difluorophenyl)ethenyl]carbamate

HRID 2088671Notes

Reaction equation

HRID 2088671 reaction equation
[Na].[NH2:2][C:3]([C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][C:8]=1[F:14])=[CH:4][C:5]#[N:6].[C:15](=O)([O:19]CC)[O:16][CH2:17][CH3:18].Cl>C(O)C.O.C(OCC)(=O)C>[CH2:17]([O:16][C:15](=[O:19])[NH:2]/[C:3](/[C:7]1[CH:12]=[CH:11][C:10]([F:13])=[CH:9][C:8]=1[F:14])=[CH:4]\[C:5]#[N:6])[CH3:18]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 7766Diethyl CarbonateHCID 5360545SodiumHCID 667253443-Amino-3-(2,4-difluorophenyl)prop-2-enenitrile

Product 1

HCID 58305996Ethyl[(Z)-2-cyano-1-(2,4-difluorophenyl)ethenyl]carbamate

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

At 40° C., 769 mg (33.44 mmol) of sodium were dissolved in ethanol (41 ml). 4.14 g (22.29 mmol) of 3-amino-3-(2,4-difluorophenyl)prop-2-enonitrile and 5.79 g (49 mmol) of diethyl carbonate were added, and the reaction solution was stirred under reflux for 4 h. 200 ml of ethyl acetate and 150 ml of water were added to the reaction mixture and the pH was adjusted with hydrochloric acid to pH=5. The organic phase was separated off, dried over magnesium sulfate and concentrated on a rotary evaporator. The residue was triturated with diisopropyl ether and the white precipitate was filtered off with suction. More product was obtained by separating the mother liquor by preparative HPLC (Method 11). Drying under high vacuum gave a total of 4.92 g (49% of theory) of the product as a mixture of E and Z isomers which was used without further purification.

Workup

  1. temperatureunder reflux for 4 h
  2. customThe organic phase was separated off
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated on a rotary evaporator
  5. customThe residue was triturated with diisopropyl ether
  6. filtrationthe white precipitate was filtered off with suction
  7. customMore product was obtained
  8. customby separating the mother liquor by preparative HPLC (Method 11)
  9. customDrying under high vacuum
  10. customgave a total of 4.92 g (49% of theory) of the product
  11. additionas a mixture of E and Z isomers which
  12. customwas used without further purification

Sources & evidence

ORD record
ord-2f4f357b73274f0f9807f875eeafd29f
Source dataset
uspto-grants-2013_05
Patent number
US08436003B2

Reaction notes

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