Hydrochloric Acid → N-[2-(3,4-dimethoxyphenyl)ethyl]-3-difluoromethoxy-2-(4-chlorophenyl)acrylamide

HRID 1884222Notes

Reaction equation

HRID 1884222 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:11][CH2:12][NH:13][C:14](=[O:25])[C:15]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)=[CH:16][OH:17])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[OH-].[K+].Cl[CH:29]([F:31])[F:30].Cl>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.COCCOC>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:11][CH2:12][NH:13][C:14](=[O:25])[C:15]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)=[CH:16][O:17][CH:29]([F:31])[F:30])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6372ChlorodifluoromethaneHCID 14797Potassium HydroxideHCID 69900553N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-chlorophenyl)acrylamide

Product 1

HCID 69900635N-[2-(3,4-dimethoxyphenyl)ethyl]-3-difluoromethoxy-2-(4-chlorophenyl)acrylamide

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

Five hundred milligrams (500 mg) of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-chlorophenyl)acrylamide (1.33 mmol), 2.00 g (3.56 mmol) of 10% aqueous potassium hydroxide solution, 87 mg (0.266 mmol) of tetrabutylammonium bromide and 10 ml of ethylene glycol dimethyl ether were mixed and chlorodifluoromethane gas was blown thereto at room temperature. After a sample was taken out from the reaction mixture and the disappearance of the starting material was confirmed by thin layer chromatograph analysis, 5% hydrochloric acid was added to the reaction mixture. The reaction mixture was extracted with ethyl acetate, washed with 5% hydrochloric acid, saturated aqueous sodium bicarbonate solution and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=2:1) and the obtained residue was washed with hexane to give 360 mg of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-difluoromethoxy-2-(4-chlorophenyl)acrylamide.

Workup

  1. customat room temperature
  2. additionwas added to the reaction mixture
  3. extractionThe reaction mixture was extracted with ethyl acetate
  4. washwashed with 5% hydrochloric acid, saturated aqueous sodium bicarbonate solution and saturated brine subsequently
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. washthe obtained residue was washed with hexane

Sources & evidence

ORD record
ord-0fffa993620646bfa650407c07bd3996
Source dataset
uspto-grants-2004_07
Patent number
US06762321B2

Reaction notes

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