Tert-butyl 3-(1-amino-2,2,2-trifluoroethyl)-5-bromobenzoate → Tert-butyl 3-(1-amino-2,2,2-trifluoroethyl)-5-(5-methylpyridin-2-yl)benzoate

HRID 888420Notes

Reaction equation

HRID 888420 reaction equation
[NH2:1][CH:2]([C:7]1[CH:8]=[C:9]([CH:17]=[C:18](Br)[CH:19]=1)[C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C:3]([F:6])([F:5])[F:4].Br[Zn][C:23]1[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][N:24]=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>[NH2:1][CH:2]([C:7]1[CH:8]=[C:9]([CH:17]=[C:18]([C:23]2[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][N:24]=2)[CH:19]=1)[C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C:3]([F:6])([F:5])[F:4]

Participants

5

Reactant 2

HCID 59539695Tert-butyl 3-(1-amino-2,2,2-trifluoroethyl)-5-bromobenzoateHCID 178427803HCID 178427803, compound

Product 1

HCID 68496539Tert-butyl 3-(1-amino-2,2,2-trifluoroethyl)-5-(5-methylpyridin-2-yl)benzoateYield 96%

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of tert-butyl 3-(1-amino-2,2,2-trifluoroethyl)-5-bromobenzoate (1.4 g, 3.95 mmol) in dioxane (20 mL) was added bis(tri-t-butylphosphine)palladium(0) (0.06 g, 0.12 mmol). The mixture was degassed with nitrogen and bromo(5-methylpyridin-2-yl)zinc (0.5 M in THF; 23.7 mL, 11.9 mmol) was added. The mixture was heated to 70° C. After 1 h, the mixture was cooled to ambient temperature and filtered with Celite. The filtrate was concentrated to remove dioxane and saturated NaHCO3 was 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% dichloromethane→60% dichloromethane/ethyl acetate) gave the title compound (1.39 g). MS 367.1 (M+1).

Workup

  1. additionwas added
  2. temperaturethe mixture was cooled to ambient temperature
  3. filtrationfiltered with Celite
  4. concentrationThe filtrate was concentrated
  5. customto remove dioxane and saturated NaHCO3
  6. additionwas added
  7. extractionThe mixture was extracted with ethyl acetate (3×)
  8. washThe combined organic extracts were washed with brine
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customPurification by silica gel chromatography (100% dichloromethane→60% dichloromethane/ethyl acetate)

Sources & evidence

ORD record
ord-eac481ddd1c14ab4a72a7c0f24373771
Source dataset
uspto-grants-2012_08
Patent number
US08247401B2

Reaction notes

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