Chlorodifluoromethane → N-[2-(4-benzyloxy-3-methoxyphenyl)-1-methylethyl]-3-difluoromethoxy-2-(4-methylphenyl)acrylamide

HRID 1884265Notes

Reaction equation

HRID 1884265 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH:16]([NH:18][C:19](=[O:30])[C:20]([C:23]2[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][CH:24]=2)=[CH:21][OH:22])[CH3:17])=[CH:11][C:10]=1[O:31][CH3:32])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[K+].Cl[CH:36]([F:38])[F:37]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.COCCOC>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH:16]([NH:18][C:19](=[O:30])[C:20]([C:23]2[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][CH:24]=2)=[CH:21][O:22][CH:36]([F:38])[F:37])[CH3:17])=[CH:11][C:10]=1[O:31][CH3:32])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 6372ChlorodifluoromethaneHCID 14797Potassium HydroxideHCID 69900484N-[2-(4-benzyloxy-3-methoxyphenyl)-1-methylethyl]-3-hydroxy-2-(4-methylphenyl)acrylamide

Product 1

HCID 69900030N-[2-(4-benzyloxy-3-methoxyphenyl)-1-methylethyl]-3-difluoromethoxy-2-(4-methylphenyl)acrylamide

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

1.90 g (4.41 mmol) of N-[2-(4-benzyloxy-3-methoxyphenyl)-1-methylethyl]-3-hydroxy-2-(4-methylphenyl)acrylamide, 0.99 g (17.6 mmol) of 10% aqueous potassium hydroxide solution, 716 mg (2.20 mmol) of tetrabutylammonium bromide and 20 ml of ethylene glycol dimethyl ether were mixed and chlorodifluoromethane gas was blown thereto at room temperature to 50° C. After a sample was taken out from the reaction mixture and the disappearance of the starting material was confirmed by thin layer chromatograph analysis, the reaction mixture was cooled. Then, 5% hydrochrolic acid was added to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochrolic acid, saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was washed with hexane to give 1.80 g of N-[2-(4-benzyloxy-3-methoxyphenyl)-1-methylethyl]-3-difluoromethoxy-2-(4-methylphenyl)acrylamide.

Workup

  1. customat room temperature to 50° C
  2. temperaturethe reaction mixture was cooled
  3. extractionby extracted with ethyl acetate
  4. washwashed with 5% hydrochrolic acid, saturated brine subsequently
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. washThe residue was washed with hexane

Sources & evidence

ORD record
ord-df8528f22b834b46a563f762975ffd76
Source dataset
uspto-grants-2004_07
Patent number
US06762321B2

Reaction notes

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