1-{4-[3-(2,6-dichloro-phenyl)-5-isopropyl-3H-[1,2,3]triazol-4-ylmethoxy]-2-methyl-phenyl}-ethanone → 2-{4-[3-(2,6-Dichloro-phenyl)-5-isopropyl-3H-[1,2,3]triazol-4-ylmethoxy]-2-methyl-phenyl}-propan-2-ol

HRID 424783Notes

Reaction equation

HRID 424783 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[N:9]1[C:13]([CH2:14][O:15][C:16]2[CH:21]=[CH:20][C:19]([C:22](=[O:24])[CH3:23])=[C:18]([CH3:25])[CH:17]=2)=[C:12]([CH:26]([CH3:28])[CH3:27])[N:11]=[N:10]1.[CH3:29][Mg]Br>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[N:9]1[C:13]([CH2:14][O:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]([OH:24])([CH3:29])[CH3:23])=[C:18]([CH3:25])[CH:17]=2)=[C:12]([CH:26]([CH3:28])[CH3:27])[N:11]=[N:10]1

Participants

4

Reactant 2

HCID 667040541-{4-[3-(2,6-dichloro-phenyl)-5-isopropyl-3H-[1,2,3]triazol-4-ylmethoxy]-2-methyl-phenyl}-ethanoneHCID 178418573HCID 178418573, compound

Product 1

HCID 667041762-{4-[3-(2,6-Dichloro-phenyl)-5-isopropyl-3H-[1,2,3]triazol-4-ylmethoxy]-2-methyl-phenyl}-propan-2-olYield 80.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a −78° C. solution of 1-{4-[3-(2,6-dichloro-phenyl)-5-isopropyl-3H-[1,2,3]triazol-4-ylmethoxy]-2-methyl-phenyl}-ethanone (500 mg, 1.19 mmol) in THF (12 mL) is added methylmagnesium bromide (2.0 mL, 5.98 mmol, 3.0 M in THF) dropwise. The reaction mixture is warmed to room temperature. After 4 h, the reaction is cooled to 0° C., quenched with NH4Cl and warmed to room temperature. The reaction mixture is concentrated and the residue is partitioned between Et2O and 1N HCl. The aqueous layer is extracted with Et2O and the combined organic layers are washed with brine, dried (MgSO4), filtered, concentrated and chromatographed eluting with 0% to 30% EtOAC/Hexane to yield the title compound (414 mg, 80%). 1H NMR (400 MHz, CDCl3) δ 7.49-7.46 (m, 2H), 7.43-7.38 (m, 1H), 7.23-7.19 (m, 2H), 6.70 (d, 1H, J=8.8 Hz), 4.89 (s, 2H), 3.20 (sept, 1H, J=6.6 Hz), 2.04 (s, 3H), 1.53 (s, 6H), 1.45 (d, 6H, J=6.6 Hz).

Workup

  1. temperaturethe reaction is cooled to 0° C.
  2. customquenched with NH4Cl
  3. temperaturewarmed to room temperature
  4. concentrationThe reaction mixture is concentrated
  5. customthe residue is partitioned between Et2O and 1N HCl
  6. extractionThe aqueous layer is extracted with Et2O
  7. washthe combined organic layers are washed with brine
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customchromatographed
  12. washeluting with 0% to 30% EtOAC/Hexane

Sources & evidence

ORD record
ord-76faa8eb6d1b4f5fa3a1391f5d5958a0
Source dataset
uspto-grants-2012_01
Patent number
US08106077B2

Reaction notes

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