Potassium Acetate → N,N-diethyl-4-hydroxy-2-(trifluoromethoxy)benzamide

HRID 1159060Notes

Reaction equation

HRID 1159060 reaction equation
[CH2:1]([N:3]([CH2:18][CH3:19])[C:4](=[O:17])[C:5]1[CH:10]=[CH:9][C:8](Br)=[CH:7][C:6]=1[O:12][C:13]([F:16])([F:15])[F:14])[CH3:2].B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)[O:21]1.C([O-])(=O)C.[K+]>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([N:3]([CH2:18][CH3:19])[C:4](=[O:17])[C:5]1[CH:10]=[CH:9][C:8]([OH:21])=[CH:7][C:6]=1[O:12][C:13]([F:16])([F:15])[F:14])[CH3:2]

Participants

6

Reactant 3

HCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 686878354-bromo-N,N-diethyl-2-(trifluoromethoxy)benzamide

Product 1

HCID 68687198N,N-diethyl-4-hydroxy-2-(trifluoromethoxy)benzamideYield 82.5%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a stirring degassed solution of N,N-diethyl-4-bromo-2-(trifluoromethoxy)benzamide (2768 mg, 8.2 mmol), bis(pinacolato)diboron (2281 mg, 9.0 mmol), and potassium acetate (2402 mg, 24.5 mmol) in dry DMF (60 mL) was added palladium(II) acetate (55 mg, 0.25 mmol). The reaction was heated to 80° C. for 2 h and then cooled to room temp. The reaction was quenched with water and extracted with EtOAc (3×75 mL). The organic layers were combined, dried over Na2SO4, and conc. in vacuo to a brown oil. The oil was dissolved in THF (40 mL) and acetic acid (2.0 mL) and treated with hydrogen peroxide (8 mL). The reaction was stirred for 15 min and then quenched with st. aq. NaHSO3. The reaction was extracted with EtOAc (3×40 mL). The organic layers were combined, dried over Na2SO4, and conc. in vacuo to a brown oil. The oil was purified by flash chromatography (silica gel, 20-70% EtOAc in hexanes) to give 1876 mg of the desired product as a white solid. MS (ESI) 278 (M+H).

Workup

  1. temperaturecooled to room temp
  2. customThe reaction was quenched with water
  3. extractionextracted with EtOAc (3×75 mL)
  4. dry with materialdried over Na2SO4
  5. dissolutionThe oil was dissolved in THF (40 mL)
  6. additionacetic acid (2.0 mL) and treated with hydrogen peroxide (8 mL)
  7. customquenched with st
  8. extractionThe reaction was extracted with EtOAc (3×40 mL)
  9. dry with materialdried over Na2SO4
  10. customThe oil was purified by flash chromatography (silica gel, 20-70% EtOAc in hexanes)

Sources & evidence

ORD record
ord-a2281878d97d4255bc70dab15c0f2a72
Source dataset
uspto-grants-2010_10
Patent number
US07812024B2

Reaction notes

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