3-(2-Chloro-4-methoxy-phenyl)-1,1,1-trifluoro-2-(5-methyl-pyrazin-2-yl)-butan-2-ol → 3-Chloro-4-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(5-methyl-pyrazin-2-yl)-propyl]-phenol

HRID 333772Notes

Reaction equation

HRID 333772 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([O:8]C)[CH:5]=[CH:4][C:3]=1[CH:10]([CH3:24])[C:11]([C:17]1[CH:22]=[N:21][C:20]([CH3:23])=[CH:19][N:18]=1)([OH:16])[C:12]([F:15])([F:14])[F:13]>Br>[Cl:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[CH:4][C:3]=1[CH:10]([CH3:24])[C:11]([OH:16])([C:17]1[CH:22]=[N:21][C:20]([CH3:23])=[CH:19][N:18]=1)[C:12]([F:15])([F:13])[F:14]

Participants

3

Reactant 1

HCID 252527573-(2-Chloro-4-methoxy-phenyl)-1,1,1-trifluoro-2-(5-methyl-pyrazin-2-yl)-butan-2-ol

Product 1

HCID 574212313-Chloro-4-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(5-methyl-pyrazin-2-yl)-propyl]-phenolYield 74.6%

Reagents, catalysts & solvents 1

HCID 260Hydrogen BromideSolvent

Procedure

A solution of 3-(2-chloro-4-methoxy-phenyl)-1,1,1-trifluoro-2-(5-methyl-pyrazin-2-yl)-butan-2-ol (Example 1, 60 mg, 0.17 mmol) in aqueous HBr (48%, 2 mL) was refluxed for 3 h. The reaction mixture was poured into ice/water, and extracted (ethyl acetate). The combined organic layers were dried (Na2SO4), filtered and evaporated. The residue was taken up in methanol and purified (reversed-phase, preparative HPLC, Agilent Zorbax XdB-C18 column, solvent gradient 5-95% CH3CN in 0.1% TFA[aq]) to give the title compound (44 mg). MS (m/e)=347.1 (MH+).

Workup

  1. extractionextracted (ethyl acetate)
  2. dry with materialThe combined organic layers were dried (Na2SO4)
  3. filtrationfiltered
  4. customevaporated
  5. custompurified (reversed-phase, preparative HPLC, Agilent Zorbax XdB-C18 column, solvent gradient 5-95% CH3CN in 0.1% TFA[aq])

Sources & evidence

ORD record
ord-4ce2e237cd764e01a5835e9d531e8f8d
Source dataset
uspto-grants-2014_11
Patent number
US08883786B2

Reaction notes

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