Tert-butyl 3-bromo-5-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]benzoate → Tert-butyl 3-(5-methylpyridin-2-yl)-5-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]benzoate

HRID 888373Notes

Reaction equation

HRID 888373 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:12]=[C:13]([C:15]([OH:24])([C:20]([F:23])([F:22])[F:21])[C:16]([F:19])([F:18])[F:17])[CH:14]=1)[C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6].[Br-].[CH3:26][C:27]1[CH:28]=[CH:29][C:30]([Zn+])=[N:31][CH:32]=1>O1CCOCC1.[Zn]>[CH3:26][C:27]1[CH:28]=[CH:29][C:30]([C:2]2[CH:3]=[C:4]([CH:12]=[C:13]([C:15]([OH:24])([C:16]([F:17])([F:18])[F:19])[C:20]([F:23])([F:21])[F:22])[CH:14]=2)[C:5]([O:7][C:8]([CH3:9])([CH3:10])[CH3:11])=[O:6])=[N:31][CH:32]=1

Participants

5

Reactant 2

HCID 86646752Tert-butyl 3-bromo-5-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]benzoateHCID 178427808HCID 178427808, compound

Product 1

HCID 86646754Tert-butyl 3-(5-methylpyridin-2-yl)-5-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]benzoate

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of tert-butyl 3-bromo-5-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]benzoate (1.2 g, 2.8 mmol) in 0.6 mL of dioxane under N2 was added 5-methyl-2-pyridyl zinc bromide (0.5M, 11.3 mL, 5.67 mmol). The reaction was heated to 70° C. for two hours. An additional 0.5 equivalents of zinc reagent was added and the mixture stirred at 70° C. overnight. The mixture was cooled and concentrated. The crude material was taken up in EtOAc and sat. NaHCO3 and sat. Rochelle's salt added. The organic layer was extracted and washed with Rochelle's salt (2×) followed by brine. The final organic layer was dried over Na2SO4, filtered and concentrated to 1.01 g of crude material. Purification using automated flash chromatography (SiO2, 120 g, 0-5% MeOH/DCM) gave, upon concentration, title product. LC-MS (M+H)=436.1

Workup

  1. temperatureThe mixture was cooled
  2. concentrationconcentrated
  3. additionsat. NaHCO3 and sat. Rochelle's salt added
  4. extractionThe organic layer was extracted
  5. washwashed with Rochelle's salt (2×)
  6. dry with materialThe final organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated to 1.01 g of crude material
  9. customPurification

Sources & evidence

ORD record
ord-203ae7a44557439585ffbcf25cd8b408
Source dataset
uspto-grants-2012_08
Patent number
US08247401B2

Reaction notes

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