Triethylamine → HCID 58136639, compound

HRID 877212Notes

Reaction equation

HRID 877212 reaction equation
Br[C:2]1[C:3]([F:9])=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].[C:10]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])(=[O:13])[CH:11]=[CH2:12].C(N(CC)CC)C.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:5][C:4]1[C:3]([F:9])=[C:2](/[CH:12]=[CH:11]/[C:10]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH:8]=[CH:7][CH:6]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 15458tert-Butyl acrylateHCID 80271Tri-o-tolylphosphineHCID 223418913-Bromo-2-fluoroaniline

Product 1

HCID 58136639HCID 58136639, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
145 °C

Procedure

400 mg (2.10 mmol) of 3-bromo-2-fluoroaniline, 809.42 mg (6.32 mmol) of tert-butyl acrylate and 1.47 ml (10.53 mmol) of triethylamine were initially charged in 2.4 ml of DMF. The reaction vessel was evacuated three times and in each case vented with argon. 47.26 mg (0.21 mmol) of palladium(II) acetate and 128.14 mg (0.42 mmol) of tri-2-tolylphosphine were then added, and the reaction vessel was evacuated two more times and again vented with argon. The mixture was stirred at 145° C. overnight. The reaction mixture was then cooled, added to saturated ammonium chloride solution and extracted three times with ethyl acetate. The combined organic phases were dried over magnesium sulfate and concentrated. The crude product was purified by preparative RP-HPLC (mobile phase: acetonitrile/water gradient). This gave 210 mg (42% of theory) of the title compound.

Workup

  1. customThe reaction vessel was evacuated three times
  2. customthe reaction vessel was evacuated two more times
  3. temperatureThe reaction mixture was then cooled
  4. additionadded to saturated ammonium chloride solution
  5. extractionextracted three times with ethyl acetate
  6. dry with materialThe combined organic phases were dried over magnesium sulfate
  7. concentrationconcentrated
  8. customThe crude product was purified by preparative RP-HPLC (mobile phase: acetonitrile/water gradient)

Sources & evidence

ORD record
ord-304f73af51db4006a6f6aa2045170a6b
Source dataset
uspto-grants-2015_03
Patent number
US08987256B2

Reaction notes

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