Hydrochloric Acid → 4-[3-(2,5-Dichloro-4,6-dimethyl-3-pyridinyl)-1,2,4-oxadiazol-5-yl]-2-methoxy-6-nitrophenol

HRID 42676Notes

Reaction equation

HRID 42676 reaction equation
[OH:1][C:2]1[C:10]([N+:11]([O-:13])=[O:12])=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[O:14][CH3:15].[Cl:16][C:17]1[N:26]=[C:25]([CH3:27])[C:24]([Cl:28])=[C:23]([CH3:29])[C:18]=1/[C:19](=[N:21]/O)/[NH2:20].N1C=CC=CC=1.Cl>S(Cl)(Cl)=O>[Cl:16][C:17]1[C:18]([C:19]2[N:20]=[C:6]([C:5]3[CH:9]=[C:10]([N+:11]([O-:13])=[O:12])[C:2]([OH:1])=[C:3]([O:14][CH3:15])[CH:4]=3)[O:8][N:21]=2)=[C:23]([CH3:29])[C:24]([Cl:28])=[C:25]([CH3:27])[N:26]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 155279394-Hydroxy-3-methoxy-5-nitrobenzoic acidHCID 462051712,5-dichloro-N-hydroxy-4,6-dimethylpyridine-3-carboximidamide

Product 1

HCID 1362385814-[3-(2,5-Dichloro-4,6-dimethyl-3-pyridinyl)-1,2,4-oxadiazol-5-yl]-2-methoxy-6-nitrophenolYield 62.7%

Reagents, catalysts & solvents 1

HCID 24386Thionyl ChlorideSolvent

Conditions

Temperature
80 °C

Procedure

A stirred suspension of 4-hydroxy-3-methoxy-5-nitrobenzoic acid (2.00 g, 9.38 mmol) in thionyl chloride (8.2 mL) was heated at 80° C. for two hours. The excess of thionyl chloride was removed under vacuum. The resulting yellow solid was dissolved in DMA (15.4 mL), then (Z)-2,5-dichloro-N′-hydroxy-4,6-dimethylnicotinimidamide (2.636 g, 11.26 mmol) and pyridine (6.2 mL) were added. The red solution was heated to 120° C. for 2.5 hours. The reaction mixture was cooled to room temperature and poured into a mixture of cc HCl (10 ml) and ice (80 g), then stirred for thirty minutes. The yellow precipitate was filtered off, washed with water and dried under vacuum. Recrystallization from dichloro-methane-iso-propanol mixture afforded 2.42 g (62%) of 4-(3-(2,5-dichloro-4,6-dimethylpyridin-3-yl)-1,2,4-oxadiazol-5-yl)-2-methoxy-6-nitrophenol as yellow crystalline.

Workup

  1. customThe excess of thionyl chloride was removed under vacuum
  2. dissolutionThe resulting yellow solid was dissolved in DMA (15.4 mL)
  3. temperatureThe red solution was heated to 120° C. for 2.5 hours
  4. temperatureThe reaction mixture was cooled to room temperature
  5. filtrationThe yellow precipitate was filtered off
  6. washwashed with water
  7. customdried under vacuum
  8. customRecrystallization from dichloro-methane-iso-propanol mixture

Sources & evidence

ORD record
ord-6143d7cb3fcb426f800819bb156f632c
Source dataset
uspto-grants-2013_09
Patent number
US08536203B2

Reaction notes

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