1-Azido-4-methoxybenzene → 5-(2-Fluoro-4-trifluoromethyl-phenyl)-3-(4-methoxy-phenyl)-3H-[1,2,3]triazol-4-ylamine

HRID 1639694Notes

Reaction equation

HRID 1639694 reaction equation
[N:1]([C:4]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[CH:6][CH:5]=1)=[N+:2]=[N-:3].[F:12][C:13]1[CH:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:16]=[CH:15][C:14]=1[CH2:23][C:24]#[N:25].C[O-].[Na+]>C(O)C>[F:12][C:13]1[CH:18]=[C:17]([C:19]([F:21])([F:22])[F:20])[CH:16]=[CH:15][C:14]=1[C:23]1[N:3]=[N:2][N:1]([C:4]2[CH:5]=[CH:6][C:7]([O:10][CH3:11])=[CH:8][CH:9]=2)[C:24]=1[NH2:25]

Participants

5

Reactant 3

HCID 750041-Azido-4-methoxybenzeneHCID 27375972-Fluoro-4-(trifluoromethyl)phenylacetonitrileHCID 10942334Sodium Methoxide

Product 1

HCID 252159065-(2-Fluoro-4-trifluoromethyl-phenyl)-3-(4-methoxy-phenyl)-3H-[1,2,3]triazol-4-ylamineYield 53.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

To an ice-cooled solution of 1-azido-4-methoxy-benzene (0.450 g, 3.0171 mmol) and commercial 2-fluoro-4-(trifluoromethyl)phenyl acetonitrile (0.736 g, 3.6205 mmol) in absolute ethanol (10 ml) and under a nitrogen flow, sodium methoxide (0.2445 g, 4.5257 mmol) in absolute ethanol (5 ml) is added drop-wise and the resulting mixture is allowed to attain room temperature spontaneously overnight. The reaction mixture is evaporated and the solid residue is dissolved in dichloromethane (80 ml) and the organic solution is washed with water (60 ml), brine (60 ml), dried over MgSO4, filtered and evaporated (˜1 g). This crude residue is purified by crystallization from a mixture of dichloromethane and petroleum ether, to afford the title compound as a yellow solid (0.570 g, 53% yield). M.p. 164.6-165.5° C. LC-ESI-HRMS of [M+H]+ shows 353.1028 Da. Calc. 353.102548 Da, dev. 0.7 ppm.

Workup

  1. customThe reaction mixture is evaporated
  2. dissolutionthe solid residue is dissolved in dichloromethane (80 ml)
  3. washthe organic solution is washed with water (60 ml), brine (60 ml)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated (˜1 g)
  7. customThis crude residue is purified by crystallization from a mixture of dichloromethane and petroleum ether

Sources & evidence

ORD record
ord-3c1d267bb40946eaa536f1f2e8afb8ef
Source dataset
uspto-grants-2012_02
Patent number
US08110588B2

Reaction notes

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