1-Azido-4-methoxybenzene → 5-(2-Chloro-4-fluoro-phenyl)-3-(4-methoxy-phenyl)-3h-[1,2,3]triazol-4-ylamine

HRID 1639703Notes

Reaction equation

HRID 1639703 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].[Cl:12][C:13]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=1[CH2:20][C:21]#[N:22].C[O-].[Na+]>C(O)C>[Cl:12][C:13]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=1[C:20]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:21]=1[NH2:22]

Participants

5

Reactant 3

HCID 750041-Azido-4-methoxybenzeneHCID 27250632-Chloro-4-fluorophenylacetonitrileHCID 10942334Sodium Methoxide

Product 1

HCID 252161595-(2-Chloro-4-fluoro-phenyl)-3-(4-methoxy-phenyl)-3h-[1,2,3]triazol-4-ylamineYield 66.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

To a stirred and ice-cooled solution of 1-azido-4-methoxy-benzene (1.000 g, 6.7046 mmol) and 2-chloro-4-fluoro phenyl acetonitrile (1.758 g, 10.0569 mmol) in absolute ethanol (15 ml), an ice-cooled solution of sodium methoxide (0.435 g, 8.0455 mmol) in absolute ethanol (10 ml) is added drop-wise. The resulting reaction mixture is evaporated and the residue is dissolved in methylene chloride and washed with water, brine, dried over MgSO4, filtered and evaporated to afford ˜2.2 g of crude material as brownish solid. This material is purified by crystallization from methylene chloride and petroleum ether, to obtain the title compound as yellowish solid (1.42 g, 66% yield). M.p. 175-176.8° C. LC-ESI-HRMS of [M+H]+ shows 319.0745 Da. Calc. 319.076192 Da, dev. −5.3 ppm.

Workup

  1. additionis added drop-wise
  2. customThe resulting reaction mixture
  3. customis evaporated
  4. dissolutionthe residue is dissolved in methylene chloride
  5. washwashed with water, brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. customto afford ˜2.2 g of crude material as brownish solid
  10. customThis material is purified by crystallization from methylene chloride and petroleum ether

Sources & evidence

ORD record
ord-9692c5b4d7fd439bb4404a2ba194e126
Source dataset
uspto-grants-2012_02
Patent number
US08110588B2

Reaction notes

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