4-Chlorobenzyl cyanide → 5-(4-Chloro-phenyl)-3-(2-fluoro-4-trifluoromethyl-phenyl)-3H-[1,2,3]triazol-4-ylamine

HRID 1639696Notes

Reaction equation

HRID 1639696 reaction equation
C[O-].[Na+].[Cl:4][C:5]1[CH:13]=[CH:12][C:8]([CH2:9][C:10]#[N:11])=[CH:7][CH:6]=1.[N:14]([C:17]1[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][C:18]=1[F:27])=[N+:15]=[N-:16]>CO>[Cl:4][C:5]1[CH:13]=[CH:12][C:8]([C:9]2[N:16]=[N:15][N:14]([C:17]3[CH:22]=[CH:21][C:20]([C:23]([F:25])([F:26])[F:24])=[CH:19][C:18]=3[F:27])[C:10]=2[NH2:11])=[CH:7][CH:6]=1

Participants

5

Reactant 3

HCID 2415824-Chlorobenzyl cyanideHCID 10942334Sodium MethoxideHCID 866450681-Azido-2-fluoro-4-(trifluoromethyl)benzene

Product 1

HCID 252159095-(4-Chloro-phenyl)-3-(2-fluoro-4-trifluoromethyl-phenyl)-3H-[1,2,3]triazol-4-ylamineYield 26.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred and ice-cooled solution of sodium methoxide (0.296 g, 5.4848 mmol) in methanol (25 ml), commercial 4-chlorobenzyl cyanide (0.610 g, 4.0222 mmol) and 1-azido-2-fluoro-4-trifluoromethyl-benzene (0.750 g, 3.6565 mmol) are added portion wise. The reaction mixture is allowed to reach room temperature spontaneously overnight, concentrated in vacuo, added water, and extracted with ethylacetate (3×80 ml). The combined organic layers are dried over MgSO4, filtered and evaporated, to afford a red solid residue (1.200 g, 92% mass balance). This crude material is purified by column chromatography over silica gel (230-400 mesh) eluting with 10% ethylacetate in petroleum ether, to obtain the title compound as an off-white solid (0.350 g, 26% yield). M.p. 169.9-170.2° C. LC-ESI-HRMS of [M+H]+ shows 357.0516 Da. Calc. 357.053011 Da, dev. −4 ppm.

Workup

  1. additionare added portion wise
  2. concentrationconcentrated in vacuo
  3. additionadded water
  4. extractionextracted with ethylacetate (3×80 ml)
  5. dry with materialThe combined organic layers are dried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. customto afford a red solid residue (1.200 g, 92% mass balance)
  9. customThis crude material is purified by column chromatography over silica gel (230-400 mesh)
  10. washeluting with 10% ethylacetate in petroleum ether

Sources & evidence

ORD record
ord-ad7eaf1127ed44f0bce387f664bbcb41
Source dataset
uspto-grants-2012_02
Patent number
US08110588B2

Reaction notes

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