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

HRID 1639705Notes

Reaction equation

HRID 1639705 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]=[CH:17][C:16]([CH2:19][C:20]#[N:21])=[C:15]([F:22])[CH:14]=1.C[O-].[Na+]>C(O)C>[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[N:3]=[N:2][N:1]([C:4]3[CH:5]=[CH:6][C:7]([O:10][CH3:11])=[CH:8][CH:9]=3)[C:20]=2[NH2:21])=[C:15]([F:22])[CH:14]=1

Participants

5

Reactant 3

HCID 750041-Azido-4-methoxybenzeneHCID 2736569(4-Chloro-2-fluoro-phenyl)-acetonitrileHCID 10942334Sodium Methoxide

Product 1

HCID 252161615-(4-Chloro-2-fluoro-phenyl)-3-(4-methoxy-phenyl)-3H-[1,2,3]triazol-4-ylamineYield 3.3%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

To a stirred and ice-cooled solution of 1-azido-4-methoxy-benzene (2.000 g, 13.4090 mmol) and commercial (4-chloro-2-fluoro-phenyl)-acetonitrile (2.729 g, 16.0909 mmol) in absolute ethanol (30 ml), an ice-cooled solution of sodium methoxide (1.087 g, 20.1136 mmol) in absolute ethanol (20 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 ˜4.3 g of crude material as brownish solid. This crude product is purified by column chromatography eluting with 25-35% ethyl acetate in hexane, to obtain the title compound as a yellow solid (0.140 g, 3.25% yield). M.p. 147.9-149.5° C. LC-ESI-HRMS of [M+H]+ shows 319.0779 Da. Calc. 319.076192 Da, dev. 5.4 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 ˜4.3 g of crude material as brownish solid
  10. customThis crude product is purified by column chromatography
  11. washeluting with 25-35% ethyl acetate in hexane

Sources & evidence

ORD record
ord-2ada73e3564f4fc5a38602f0b7980d2c
Source dataset
uspto-grants-2012_02
Patent number
US08110588B2

Reaction notes

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