Sodium Azide → 5-[1-(4-chloro-benzyl)-1H-[1,2,3]triazol-4-yl]-2-methyl-phenol

HRID 2081092Notes

Reaction equation

HRID 2081092 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH3:9])=[C:5]([O:10]COC)[CH:4]=1)#[CH:2].[Cl:14][C:15]1[CH:22]=[CH:21][C:18]([CH2:19]Br)=[CH:17][CH:16]=1.[N-:23]=[N+:24]=[N-:25].[Na+]>O.C(O)(C)(C)C.[Cu].S([O-])([O-])(=O)=O.[Cu+2]>[Cl:14][C:15]1[CH:22]=[CH:21][C:18]([CH2:19][N:23]2[CH:2]=[C:1]([C:3]3[CH:8]=[CH:7][C:6]([CH3:9])=[C:5]([OH:10])[CH:4]=3)[N:25]=[N:24]2)=[CH:17][CH:16]=1

Participants

8

Reactant 3

HCID 33557Sodium AzideHCID 693291-(Bromomethyl)-4-chlorobenzeneHCID 59649717HCID 59649717, compound

Product 1

HCID 596497195-[1-(4-chloro-benzyl)-1H-[1,2,3]triazol-4-yl]-2-methyl-phenol

Reagents, catalysts & solvents 4

HCID 23978CopperCatalystHCID 24462Copper SulfateCatalystHCID 962WaterSolventHCID 6386tert-ButanolSolvent

Conditions

Temperature
130 °C

Procedure

To a suspension of 4-ethynyl-2-methoxymethoxy-1-methyl-benzene (1.50 g, 8.50 mmol) (from Example 19 supra), 4-chlorobenzyl bromide (1.76 g, 8.50 mmol) and sodium azide (0.56 g, 8.50 mmol) in a mixture of water (12 mL) and t-butanol (12 mL) was added copper powder (0.40 g, 6.30 mmol) and aqueous solution of copper sulphate solution (1 N, 1.64 mL). The reaction mixture was heated at 130° C. for 30 minutes in a microwave reactor. After cooling, the reaction mixture was partitioned between dichloromethane and water. The aqueous phase was extracted with dichloromethane (2×). The combined organic phase washed with water and brine, dried (MgSO4) and concentrated. The residue was purified by flash chromatography eluting with 40% ethyl acetate in hexanes to give 5-[1-(4-chloro-benzyl)-1H-[1,2,3]triazol-4-yl]-2-methyl-phenol; (Yield 0.75 g, 59%); and 1-(4-chloro-benzyl)-4-(3-methoxymethoxy-4-methyl-phenyl)-1H[1,2,3]triazole. (Yield 0.61 g, 21%).

Workup

  1. temperatureAfter cooling
  2. customthe reaction mixture was partitioned between dichloromethane and water
  3. extractionThe aqueous phase was extracted with dichloromethane (2×)
  4. washThe combined organic phase washed with water and brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography
  8. washeluting with 40% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-e31ed09139d447759f81bfcb8bed9fb1
Source dataset
uspto-grants-2011_04
Patent number
US07932390B2

Reaction notes

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