Dichloromethane → N'-[6-(4-chloro-3-trifluoromethyl-phenoxy)-5-methyl-pyridin-3-yl]-N-ethyl-N-pyridin-2-yl-formamidine

HRID 508471Notes

Reaction equation

HRID 508471 reaction equation
[CH3:1][N:2]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][N:6]=1)[CH:3]=O.[Cl:11][C:12]1[CH:26]=[CH:25][C:15]([O:16][C:17]2[N:22]=[CH:21][C:20]([NH2:23])=[CH:19][C:18]=2[CH3:24])=[CH:14][C:13]=1[C:27]([F:30])([F:29])[F:28].[OH-].[Na+].Cl[CH2:34]Cl>>[Cl:11][C:12]1[CH:26]=[CH:25][C:15]([O:16][C:17]2[N:22]=[CH:21][C:20]([N:23]=[CH:1][N:2]([CH2:3][CH3:34])[C:5]3[CH:10]=[CH:9][CH:8]=[CH:7][N:6]=3)=[CH:19][C:18]=2[CH3:24])=[CH:14][C:13]=1[C:27]([F:30])([F:28])[F:29]

Participants

5

Reactant 4

HCID 6344Dichloromethane2×HCID 14798Sodium HydroxideHCID 572611N-Methyl-N-(pyridine-2-yl)formamideHCID 581533506-(4-Chloro-3-trifluoromethyl-phenoxy)-5-methyl-pyridin-3-ylamine

Product 1

HCID 66940279N'-[6-(4-chloro-3-trifluoromethyl-phenoxy)-5-methyl-pyridin-3-yl]-N-ethyl-N-pyridin-2-yl-formamidine

Procedure

In a 25 ml single-necked round-bottomed flask, N-methyl-N-pyridin-2-yl-formamide (0.5 ml) is solubilized in dry dichloromethane (4 ml) at ambient temperature (colourless solution). Under stirring phosphorous oxide chloride (0.4 ml) is added dropwise by syringe. Stirring at ambient temperature is continued for 1 hour. To this solution, 6-(4-Chloro-3-trifluoromethyl-phenoxy)-5-methyl-pyridin-3-ylamine (0.6 g) dissolved in 1.0 ml of dry dichloromethane is added dropwise by syringe, giving a yellow solution. Stirring is continued at an ambient temperature for 1 hour. The mixture is then poured into ice/water (pH=2, water phase). 2 M aqueous NaOH is then added to get a pH of about 11 and stirring is continued for 10 minutes. The mixture is then extracted with dichloromethane (2×50 ml). The combined organic phases are then dried over sodium sulfate, filtered and the solvent is removed in vacuo. Purification of this gum by flash chromatography over silica gel with hexane/ethyl acetate 1:1 (v:v) gives 0.33 g of the compound as a yellow oil.

Workup

  1. additionUnder stirring phosphorous oxide chloride (0.4 ml) is added dropwise by syringe
  2. additionis added dropwise by syringe
  3. customgiving a yellow solution
  4. stirringStirring
  5. waitis continued at an ambient temperature for 1 hour
  6. customto get a pH of about 11
  7. stirringstirring
  8. waitis continued for 10 minutes
  9. extractionThe mixture is then extracted with dichloromethane (2×50 ml)
  10. dry with materialThe combined organic phases are then dried over sodium sulfate
  11. filtrationfiltered
  12. customthe solvent is removed in vacuo
  13. customPurification of this gum by flash chromatography over silica gel with hexane/ethyl acetate 1:1 (v:v)

Sources & evidence

ORD record
ord-8bd4f49c935c4bfdb1dd4496d7c5b41a
Source dataset
uspto-grants-2015_08
Patent number
US09096525B2

Reaction notes

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