Tert-butyl 3-bromo-5-(2,2,2-trifluoro-1-hydroxyethyl)benzoate → Tert-butyl 3-(5-methylpyridin-2-yl)-5-(2,2,2-trifluoro-1-hydroxyethyl)benzoate

HRID 888365Notes

Reaction equation

HRID 888365 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:12]=[C:13]([CH:15]([OH:20])[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-].[CH3:22][C:23]1[CH:24]=[CH:25][C:26]([Zn+])=[N:27][CH:28]=1>O1CCOCC1.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[CH3:22][C:23]1[CH:24]=[CH:25][C:26]([C:2]2[CH:3]=[C:4]([CH:12]=[C:13]([CH:15]([OH:20])[C:16]([F:19])([F:18])[F:17])[CH:14]=2)[C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6])=[N:27][CH:28]=1

Participants

5

Reactant 2

HCID 59539580Tert-butyl 3-bromo-5-(2,2,2-trifluoro-1-hydroxyethyl)benzoateHCID 178427808HCID 178427808, compound2×

Product 1

HCID 68500334Tert-butyl 3-(5-methylpyridin-2-yl)-5-(2,2,2-trifluoro-1-hydroxyethyl)benzoate

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalyst2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of tert-butyl 3-bromo-5-(2,2,2-trifluoro-1-hydroxyethyl)benzoate (5.0 g, 14.1 mmol) and bis(tri-tert-butylphosphine)palladium(0) (0.22 g, 0.42 mmol) in dioxane (70 mL) was added 5-methyl-2-pyridylzinc bromide (0.5 M in THF; 56.3 mL, 28.2 mmol). The reaction mixture was heated to 70° C. After 1 h, additional 5-methyl-2-pyridylzinc bromide (0.5 M in THF; 10 mL, 5.0 mmol) and bis(tri-tert-butylphosphine)palladium(0) (40 mg, 0.078 mmol) were added. After 30 min, the reaction was concentrated. Saturated aqueous sodium potassium tartrate tetrahydrate and saturated aqueous sodium bicarbonate were added. The mixture was extracted with ethyl acetate (3×). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% hexanes→70% hexanes/ethyl acetate) gave the title compound. MS 368.2 (M+1).

Workup

  1. waitAfter 30 min
  2. concentrationthe reaction was concentrated
  3. additionSaturated aqueous sodium potassium tartrate tetrahydrate and saturated aqueous sodium bicarbonate were added
  4. extractionThe mixture was extracted with ethyl acetate (3×)
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification by silica gel chromatography (100% hexanes→70% hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-84c672b5097f4cbe81c742a78935b181
Source dataset
uspto-grants-2012_08
Patent number
US08247401B2

Reaction notes

Loading…