Sodium Hydroxide → N'-[6-(4-chloro-3-trifluoromethyl-phenoxy)-4-methyl-pyridin-3-yl]-N-methyl-N-(1-methyl-prop-2-ynyl)-formamidine

HRID 1894657Notes

Reaction equation

HRID 1894657 reaction equation
[CH3:1][N:2]([CH:5]([CH3:8])[C:6]#[CH:7])[CH:3]=O.[Cl-].[P+]=O.[Cl:12][C:13]1[CH:27]=[CH:26][C:16]([O:17][C:18]2[N:23]=[CH:22][C:21]([NH2:24])=[C:20]([CH3:25])[CH:19]=2)=[CH:15][C:14]=1[C:28]([F:31])([F:30])[F:29].[OH-].[Na+]>ClCCl>[Cl:12][C:13]1[CH:27]=[CH:26][C:16]([O:17][C:18]2[N:23]=[CH:22][C:21]([N:24]=[CH:3][N:2]([CH3:1])[CH:5]([CH3:8])[C:6]#[CH:7])=[C:20]([CH3:25])[CH:19]=2)=[CH:15][C:14]=1[C:28]([F:31])([F:29])[F:30]

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 12787250N-Methyl-N-(1-methyl-prop-2-ynyl)-formamideHCID 58153450HCID 58153450, compoundHCID 178527006HCID 178527006, compound

Product 1

HCID 25158515N'-[6-(4-chloro-3-trifluoromethyl-phenoxy)-4-methyl-pyridin-3-yl]-N-methyl-N-(1-methyl-prop-2-ynyl)-formamidineYield 50%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

In a 25 ml single-necked round-bottomed flask, N-Methyl-N-(1-methyl-prop-2-ynyl)-formamide (223 mg) is solubilized in dry dichloromethane (4 ml) at ambient temperature (colourless solution). Under stirring a mixture of phosphorous oxide chloride (0.18 ml) in dichloromethane (1 ml) is added dropwise by syringe. Stirring at ambient temperature is continued for 1 hour. To this solution, 6-(4-Chloro-3-trifluoromethyl-phenoxy)-4-methyl-pyridin-3-ylamine (303 mg) dissolved in 10 ml of dry dichloromethane is added dropwise by syringe, giving a yellow solution. Stirring is continued at an ambient temperature for 3 hours. 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 3:2 (v:v) gives 198 mg of the compound as a brownish oil.

Workup

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

Sources & evidence

ORD record
ord-ca62f4d921574ee3a60e28bb50964d9c
Source dataset
uspto-grants-2013_08
Patent number
US08513286B2

Reaction notes

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