Dimethylformamide → 3-difluoromethoxy-N-[2-{3-methoxy-4-(2-propynyloxy) phenyl}ethyl]-2-(4-methylphenyl)acrylamide

HRID 1884235Notes

Reaction equation

HRID 1884235 reaction equation
[F:1][CH:2]([F:27])[O:3][CH:4]=[C:5]([C:20]1[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][CH:21]=1)[C:6]([NH:8][CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([OH:17])=[C:13]([O:18][CH3:19])[CH:12]=1)=[O:7].CN(C)C=O.Cl[CH2:34][C:35]#[CH:36].[H-].[Na+]>O>[F:1][CH:2]([F:27])[O:3][CH:4]=[C:5]([C:20]1[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][CH:21]=1)[C:6]([NH:8][CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:36][C:35]#[CH:34])=[C:13]([O:18][CH3:19])[CH:12]=1)=[O:7]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 122213-Chloro-1-propyneHCID 24758Sodium hydrideHCID 698987623-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(4-methylphenyl)acrylamide

Product 1

HCID 865899943-difluoromethoxy-N-[2-{3-methoxy-4-(2-propynyloxy) phenyl}ethyl]-2-(4-methylphenyl)acrylamideYield 43.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Five hundred milligrams (500 mg) of 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(4-methylphenyl)acrylamide (1.33 mmol), 5 ml of anhydrous N,N-dimethylformamide, 196 mg (2.65 mmol) of 3-chloropropyne and 60 mg (1.46 mmol) of 60% sodium hydride were stirred at room temperature for 2 hours. Water was added to to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochrolic 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 column chromatography (eluent, hexane:ethyl acetate=2:1) to give 242 mg of 3-difluoromethoxy-N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-2-(4-methylphenyl)acrylamide (the present compound 1353).

Workup

  1. extractionby extracted with ethyl acetate
  2. washwashed with 5% hydrochrolic acid, saturated aqueous sodium bicarbonate solution and saturated brine subsequently
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-bf80229ea9574309a424c25ff5542e74
Source dataset
uspto-grants-2004_07
Patent number
US06762321B2

Reaction notes

Loading…