Formaldehyde → 1-((3-fluoroanilino)methyl)-1H-benzotriazole

HRID 2036166Notes

Reaction equation

HRID 2036166 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].[CH2:9]=[O:10].[NH:11]1[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[N:13]=[N:12]1>>[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH:5][CH3:14].[OH:10][CH2:9][N:11]1[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[N:13]=[N:12]1.[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH:5][CH2:9][N:11]1[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[N:13]=[N:12]1

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 97423-FluoroanilineHCID 178418385HCID 178418385, compound

Product 3

HCID 2241691H-Benzotriazole-1-methanolHCID 27590113-fluoro-N-methylanilineHCID 39810541-((3-fluoroanilino)methyl)-1H-benzotriazoleYield 86.6%

Procedure

3-Fluoro-N-methylaniline was prepared from 3-fluoroaniline using a modified reductive amination. First, 1-hydroxymethylbenzotriazole was prepared by adding 37% aqueous formaldehyde to benzotriazole at 40° C. in a 1:1 ratio and cooling to room temperature to precipitate the product. After filtration the hydroxymethylbenzotriazole (125 g) was heated to reflux in toluene with 3-fluoroaniline (92.2 g). Water was removed azeotropically using a Dean-Stark trap. After three hours, the mixture was cooled to room temperature, then refrigerated for several hours to complete precipitation. The white crystalline solid was collected by filtration, yielding 174.2 g (86.6%) of 1-((3-fluoroanilino)methyl)-1H-benzotriazole.

Workup

  1. customto precipitate the product
  2. filtrationAfter filtration the hydroxymethylbenzotriazole (125 g)
  3. temperaturewas heated
  4. temperatureto reflux in toluene with 3-fluoroaniline (92.2 g)
  5. customWater was removed azeotropically
  6. temperaturethe mixture was cooled to room temperature
  7. waitrefrigerated for several hours
  8. customprecipitation
  9. filtrationThe white crystalline solid was collected by filtration

Sources & evidence

ORD record
ord-399cfed594c0434b9cb0d0dd2e3ec5c3
Source dataset
uspto-grants-2013_11
Patent number
US08575169B2

Reaction notes

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