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M-Cresol → N-(4-methylphenyl)-4-methoxy-6-(3-methylphenoxy)-2-pyridine carboxamide

HRID 1250490
Notes
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Reaction equation

HRID 1250490 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[CH:6][CH:7]=1.[H-].[Na+].[CH3:11][C:12]1[CH:17]=[CH:16][C:15]([NH:18][C:19]([C:21]2[CH:26]=[C:25]([O:27][CH3:28])[CH:24]=[C:23](Br)[N:22]=2)=[O:20])=[CH:14][CH:13]=1>CN(C=O)C.CCCCCC.[Cu](Cl)Cl>[CH3:11][C:12]1[CH:13]=[CH:14][C:15]([NH:18][C:19]([C:21]2[CH:26]=[C:25]([O:27][CH3:28])[CH:24]=[C:23]([O:8][C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([CH3:1])[CH:3]=3)[N:22]=2)=[O:20])=[CH:16][CH:17]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 3

HCID 342M-CresolHCID 24758Sodium hydrideHCID 18326207N-(4-methylphenyl)-6-bromo-4-methoxy-2-pyridine carboxamide

Product 1

HCID 15906600N-(4-methylphenyl)-4-methoxy-6-(3-methylphenoxy)-2-pyridine carboxamide

Reagents, catalysts & solvents 3

HCID 24014Cupric ChlorideCatalyst
HCID 6228
Dimethylformamide
Solvent
HCID 8058HexaneSolvent

Conditions

Temperature
100 °C

Procedure

0.45 g (0.0019×2.2 mol) of 3-methyl phenol was dissolved in about 10 ml of DMF. The obtained solution was further mixed with 0.15 g (ca. 60% in mineral oil; 0.0019×2.0 mol) of NaH and then with 0.60 g (0.0019 mol) of N-(4-methylphenyl)-6-bromo-4-methoxy-2-pyridine carboxamide. After adding 0.19 g (0.0019×1.0 mol) of copper chloride (I), the solution was stirred at about 100° C. for about 4 hours, and then allowed to stand for cooling to room temperature. After the reaction solution was distributed in hexane-saturated sodium bicarbonate water, the organic phase of the solution was washed with saturated brine and dried with anhydrous sodium sulfate, followed by concentration thereof. Thereafter, the concentrated solution was purified by silica gel column chromatography (eluting solution: ethyl acetate/hexane), thereby obtaining an aimed product.

Workup

  1. temperaturefor cooling to room temperature
  2. washthe organic phase of the solution was washed with saturated brine
  3. dry with materialdried with anhydrous sodium sulfate
  4. concentrationfollowed by concentration
  5. customThereafter, the concentrated solution was purified by silica gel column chromatography (eluting solution: ethyl acetate/hexane)

Sources & evidence

ORD record
ord-4e8cf4c5f1fb4848b7d607c7c9bd8232
Source dataset
uspto-grants-2002_01
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US06339045B1

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes