Pyridine → N-(3,5-dichloro-2-hydroxy-4-methylphenyl)-3,5-dimethoxybenzamide

HRID 505001Notes

Reaction equation

HRID 505001 reaction equation
[NH2:1][C:2]1[C:7]([OH:8])=[C:6]([Cl:9])[C:5]([CH3:10])=[C:4]([Cl:11])[CH:3]=1.N1C=CC=CC=1.[CH3:18][O:19][C:20]1[CH:21]=[C:22]([CH:26]=[C:27]([O:29][CH3:30])[CH:28]=1)[C:23](Cl)=[O:24].CC(C)=O.C(Cl)Cl>C(OCC)(=O)C>[Cl:9][C:6]1[C:7]([OH:8])=[C:2]([NH:1][C:23](=[O:24])[C:22]2[CH:26]=[C:27]([O:29][CH3:30])[CH:28]=[C:20]([O:19][CH3:18])[CH:21]=2)[CH:3]=[C:4]([Cl:11])[C:5]=1[CH3:10]

Participants

6

Reactant 4

HCID 1049PyridineHCID 870033,5-Dimethoxybenzoyl chlorideHCID 1702242-Amino-4,6-dichloro-5-methylphenolHCID 21584124Propan-2-one--dichloromethane (1/1)

Product 1

HCID 86621796N-(3,5-dichloro-2-hydroxy-4-methylphenyl)-3,5-dimethoxybenzamideYield 48%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

Into a 500 ml 3-necked round bottom flask, equipped with a stir bar, addition funnel, and N2 inlet, was placed 10 g (52 mmoles) of 6-amino-2,4-dichloro-3-methylphenol and 150 ml of ethyl acetate. With stirring a solution resulted. To this solution was added 4.53 g (57.2 mmoles) of pyridine. This solution was stirred for 5 minutes during which time 10.95 g (54.6 mmoles) of 3,5-dimethoxybenzoyl chloride (Aldrich Chemical Co., CAS RN 17213-57-9) was dissolved in 75 ml of ethyl acetate and placed in an addition funnel. This solution was added dropwise to the reaction vessel over a 30 minute period. A precipitate formed almost immediately. After complete addition the reaction mixture was allowed to stir overnight. Thin layer chromatography (5/95 acetone/CH2Cl2) analysis of the reaction mixture indicated no starting material and primarily one new spot and a spot at the origin. The reaction mixture was poured into a separatory funnel and washed 2 times with a cold 10% hydrochloric acid solution followed by 2 times with a saturated sodium chloride solution and the organic layer was dried over sodium sulfate. The sodium sulfate was collected on a gravity filter and the filtrate was concentrated to a salmon colored solid. This solid was recrystallized from refluxing ethanol. The resulting crystals were collected on a medium sintered glass funnel, and dried by sucking air through for three hours. 8.9 g of desired product was obtained, a 48% purified yield.

Workup

  1. customInto a 500 ml 3-necked round bottom flask, equipped with a stir bar, addition funnel, and N2 inlet
  2. customresulted
  3. customplaced in an addition funnel
  4. additionThis solution was added dropwise to the reaction vessel over a 30 minute period
  5. customA precipitate formed almost immediately
  6. additionAfter complete addition the reaction mixture
  7. stirringto stir overnight
  8. additionThe reaction mixture was poured into a separatory funnel
  9. washwashed 2 times with a cold 10% hydrochloric acid solution
  10. dry with materialthe organic layer was dried over sodium sulfate
  11. customThe sodium sulfate was collected on a gravity
  12. filtrationfilter
  13. concentrationthe filtrate was concentrated to a salmon
  14. customThis solid was recrystallized
  15. temperaturefrom refluxing ethanol
  16. customThe resulting crystals were collected on a medium sintered glass funnel
  17. customdried
  18. customthrough for three hours

Sources & evidence

ORD record
ord-7c919ea98f5e4c809f7be5ef15321aa7
Source dataset
uspto-grants-2010_08
Patent number
US07781373B2

Reaction notes

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