Hydrochloric Acid → 1-[4-(5-acetyl-2-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethylpentyl]-1H-quinolin-4-one

HRID 2106019Notes

Reaction equation

HRID 2106019 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.[CH:32]([O:34]CCCC)=[CH2:33].C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C([O-])([O-])=O.[K+].[K+].Cl>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2].O>[C:32]([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:25])([F:26])[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)(=[O:34])[CH3:33]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 8108Butyl vinyl etherHCID 11430Potassium CarbonateHCID 812191,3-Bis(diphenylphosphino)propaneHCID 578097571-[4-(5-bromo-2-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethylpentyl]-1H-quinolin-4-one

Product 1

HCID 578098551-[4-(5-acetyl-2-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethylpentyl]-1H-quinolin-4-oneYield 27.1%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

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), 1-vinyloxybutane (0.26 mL, 2.0 mmol), Pd(OAc)2 (5 mg, 0.02 mmol), 1,3-bis(diphenylphosphino) propane (DPPP) (10.5 mg, 0.03 mmol), K2CO3 (66.34 mg, 0.48 mmol), and water (0.1 mL) in DMF (1 mL) was microwaved for 1 hour at 122° C. After cooling, the mixture was poured into 5 mL of 5% HCl, stirred for 30 minutes and extracted with three 10 mL portions of ethyl acetate. The combined organic layers were washed with 10% aqueous K2CO3 and dried. The residue was purified silica gel chromatography and then by reverse phase HPLC to yield 50 mg (27% yield) of 1-[4-(5-acetyl-2-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethylpentyl]-1H-quinolin-4-one as white solid.

Workup

  1. customwas microwaved for 1 hour at 122° C
  2. temperatureAfter cooling
  3. extractionextracted with three 10 mL portions of ethyl acetate
  4. washThe combined organic layers were washed with 10% aqueous K2CO3
  5. customdried
  6. customThe residue was purified silica gel chromatography

Sources & evidence

ORD record
ord-9ee1034942cd4f6e80674c083934790b
Source dataset
uspto-grants-2009_08
Patent number
US07579469B2

Reaction notes

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