Phenylboronic Acid → 1-[2-hydroxy-4-(4-methoxybiphenyl-3-yl)-4-methyl-2-trifluoromethylpentyl]-1H-quinolin-4-one

HRID 2106018Notes

Reaction equation

HRID 2106018 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([O:30][CH3:31])=[C:6]([C:8]([CH3:29])([CH3:28])[CH2:9][C:10]([OH:27])([C:23]([F:26])([F:25])[F:24])[CH2:11][N:12]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15](=[O:22])[CH:14]=[CH:13]2)[CH:7]=1.[F-].[K+].[C:34]1(B(O)O)[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1>C1(C)C=CC=CC=1.C1COCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[OH:27][C:10]([C:23]([F:26])([F:25])[F:24])([CH2:9][C:8]([C:6]1[CH:7]=[C:2]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH:3]=[CH:4][C:5]=1[O:30][CH3:31])([CH3:29])[CH3:28])[CH2:11][N:12]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:15](=[O:22])[CH:14]=[CH:13]1

Participants

6

Reactant 3

HCID 66827Phenylboronic AcidHCID 522689Potassium FluorideHCID 578097571-[4-(5-bromo-2-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethylpentyl]-1H-quinolin-4-one

Product 1

HCID 578097641-[2-hydroxy-4-(4-methoxybiphenyl-3-yl)-4-methyl-2-trifluoromethylpentyl]-1H-quinolin-4-one

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 22635083Tetrahydrofuran tolueneSolvent

Procedure

A mixture of 1-[4-(5-bromo-2-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethylpentyl]-1H-quinolin-4-one (200 mg, 0.4 mmol), Pd(OAc)2 (9 mg, 0.04 mmol), DCyBPP ((2-dicyclohexylphosphino)biphenyl, 28 mg, 0.08 mmol), KF (93 mg, 1.6 mmol) in toluene/THF (3/2 mL) at room temperature was treated with phenylboronic acid (98 mg, 0.8 mmol). The reaction mixture stirred overnight at room temperature and filtered through CELITE® filter aid. The residue was diluted with EtOAc (20 mL), washed with aqueous NaOH (11.0M, 10 mL), water, and brine (10 mL). The organic phase was dried over sodium sulfate, filtered, and solvent was evaporated in vacuo. The residue was purified silica gel chromatography and then by reverse phase HPLC to provide 1-[2-hydroxy-4-(4-methoxybiphenyl-3-yl)-4-methyl-2-trifluoromethylpentyl]-1H-quinolin-4-one as white solid.

Workup

  1. filtrationfiltered through CELITE®
  2. filtrationfilter aid
  3. additionThe residue was diluted with EtOAc (20 mL)
  4. washwashed with aqueous NaOH (11.0M, 10 mL), water, and brine (10 mL)
  5. dry with materialThe organic phase was dried over sodium sulfate
  6. filtrationfiltered
  7. customsolvent was evaporated in vacuo
  8. customThe residue was purified silica gel chromatography

Sources & evidence

ORD record
ord-35bcc51e6d964061b53a613272ba5d26
Source dataset
uspto-grants-2009_08
Patent number
US07579469B2

Reaction notes

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