Hydrochloric Acid → 5-Chloro-2-(trifluoromethoxy)benzylalcohol

HRID 1819400Notes

Reaction equation

HRID 1819400 reaction equation
N(OC(C)(C)C)=O.N[C:9]1[CH:10]=[CH:11][C:12]([O:17][C:18]([F:21])([F:20])[F:19])=[C:13]([CH2:15][OH:16])[CH:14]=1.[ClH:22]>C(#N)C.[Cu](Cl)Cl>[Cl:22][C:9]1[CH:10]=[CH:11][C:12]([O:17][C:18]([F:21])([F:20])[F:19])=[C:13]([CH2:15][OH:16])[CH:14]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 10906Tert-Butyl nitriteHCID 22311140(5-Amino-2-trifluoromethoxy-phenyl)-methanol

Product 1

HCID 573686245-Chloro-2-(trifluoromethoxy)benzylalcoholYield 66%

Reagents, catalysts & solvents 2

HCID 24014Cupric ChlorideCatalystHCID 6342AcetonitrileSolvent2×

Procedure

t-Butyl nitrite (2.49 g, 24.2 mmol), copper (II) chloride (2.71 g, 20.2 mmol), and acetonitrile (100 mL) were added to a round-bottom flask. The resulting mixture was cooled to 0° C. (5-Amino-2-trifluoromethoxy-phenyl)-methanol (1.67 g, 8.1 mmol) in acetonitrile (10 mL) was slowly added to the reaction over a period of 5 min. The reaction was warmed up to room temperature and stirred overnight. The mixture was then poured into 20% HCl (100 mL) and extracted with ether (100 mL). The organic layer was washed with 20% HCl (100 mL) and dried over MgSO4. The ether was removed in vacuo and the residue was chromatographed with 4:1 hexanes:EtOAC to give 1.2 g (66%) of (5-chloro-2-trifluoromethoxy-phenyl)-methanol as a yellow solid.

Workup

  1. additionwas slowly added to the reaction over a period of 5 min
  2. extractionextracted with ether (100 mL)
  3. washThe organic layer was washed with 20% HCl (100 mL)
  4. dry with materialdried over MgSO4
  5. customThe ether was removed in vacuo
  6. customthe residue was chromatographed with 4:1 hexanes

Sources & evidence

ORD record
ord-8d2751ff9c3c4f11b4617cd21b0da05f
Source dataset
uspto-grants-2009_10
Patent number
US07601714B2

Reaction notes

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