Trifluoroacetic acid → HCID 3488428, compound

HRID 1157163Notes

Reaction equation

HRID 1157163 reaction equation
C(O[C:6]([N:8]1[CH2:13][CH:12]2[CH2:14][CH:9]1[CH2:10][NH:11]2)=O)(C)(C)C.[F:15][C:16]1[CH:17]=C(Br)[CH:19]=[CH:20][CH:21]=1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.CC(C)([O-])C.[Na+].C(O)(C(F)(F)F)=O>C1(C)C=CC=CC=1>[F:15][C:16]1[CH:17]=[C:6]([N:8]2[CH2:13][CH:12]3[CH2:14][CH:9]2[CH2:10][NH:11]3)[CH:19]=[CH:20][CH:21]=1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 140821-Bromo-3-fluorobenzeneHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 2760898(1S,4S)-tert-butyl 2,5-diazabicyclo(2.2.1)heptane-2-carboxylateHCID 23676156Sodium t-butoxide

Product 1

HCID 3488428HCID 3488428, compoundYield 62.4%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a mixture containing 2,5-Diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (100 mg, 0.5 mmol), 3-fluoro-phenylbromide (103.8 mg, 0.6 mmol), Pd(AcO) (8 mg, 0.03 mmol), 2-(di-t-butylphosphino)biphenyl (20 mg, 0.07 mmol) and sodium t-butoxide (100 mg, 1 mmol) in toluene (3 mL) was degassed with Ar. The reaction mixture was heated at 50 C for overnight. At the end of reaction, ethyl acetate was added and the mixture was filter through celite. After removal of solvent, TFA was added to the residue. The reaction mixture was stirred at ambient temperature for 1 hour. The excess TFA was removed under vacuum and the residue was purified using prep-HPLC to give desired product (60 mg, 41% yield for two steps) as TFA salt.

Workup

  1. customwas degassed with Ar
  2. temperatureThe reaction mixture was heated at 50 C for overnight
  3. customAt the end of reaction, ethyl acetate
  4. additionwas added
  5. filtrationthe mixture was filter through celite
  6. customAfter removal of solvent, TFA
  7. additionwas added to the residue
  8. customThe excess TFA was removed under vacuum
  9. customthe residue was purified

Sources & evidence

ORD record
ord-96c7136eb2514ba9bee28e8235341675
Source dataset
uspto-grants-2010_10
Patent number
US07807672B2

Reaction notes

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