1-(Azidomethyl)-4-methoxybenzene → 2-chloro-4-[1-(4-methoxybenzyl)-1H-1,2,3-triazol-4-yl]pyrimidine

HRID 410417Notes

Reaction equation

HRID 410417 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([C:8]#[CH:9])[CH:5]=[CH:4][N:3]=1.[N:10]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=1)=[N+:11]=[N-:12].O=C1O[C@H]([C@H](CO)O)C([O-])=C1O.[Na+]>O.O.O.O.O.S([O-])([O-])(=O)=O.[Cu+2].O.CC(O)(C)C>[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[N:12]=[N:11][N:10]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=3)[CH:9]=2)[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 109317671-(Azidomethyl)-4-methoxybenzeneHCID 23667548Sodium AscorbateHCID 450803662-Chloro-4-ethynylpyrimidine

Product 1

HCID 772310702-chloro-4-[1-(4-methoxybenzyl)-1H-1,2,3-triazol-4-yl]pyrimidineYield 60.6%

Reagents, catalysts & solvents 2

HCID 24463Copper sulfate pentahydrateCatalystHCID 714019492-Methylpropan-2-ol--water (1/1)Solvent

Procedure

To a solution of 2-chloro-4-ethynylpyrimidine (200 mg, 1.4 mmol) and 1-(azidomethyl)-4-methoxybenzene (0.5 M in t-butanol, 2.9 mL, 1.44 mmol) in 1:1 water tBuOH (7.2 mL) was added copper(II) sulfate pentahydrate (36 mg, 0.14 mmol) and sodium ascorbate (143 mg, 0.72 mmol) and the reaction was stirred at room temperature for 2 hrs. The reaction was then partitioned between water (50 mL) and EtOAc (50 mL). The layers were separated and the aqueous phase was extracted once with EtOAc (50 mL). The combined organic phases were washed with saturated aqueous sodium chloride (50 mL), dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure. Purification on silica (30-50% ethyl acetate in hexanes) afforded 2-chloro-4-[1-(4-methoxybenzyl)-1H-1,2,3-triazol-4-yl]pyrimidine (256 mg, 59%) as a white solid.

Workup

  1. customThe reaction was then partitioned between water (50 mL) and EtOAc (50 mL)
  2. customThe layers were separated
  3. extractionthe aqueous phase was extracted once with EtOAc (50 mL)
  4. washThe combined organic phases were washed with saturated aqueous sodium chloride (50 mL)
  5. dry with materialdried over anhydrous MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification on silica (30-50% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-fae22cc247dd496c9aa13af23bd5a781
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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