Sodium Carbonate → 1-[2-hydroxy-4-(2-methoxy-5-thiophen-3-ylphenyl)-4-methyl-2-trifluoromethylpentyl]-1H-quinolin-4-one

HRID 2106016Notes

Reaction equation

HRID 2106016 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.[S:32]1[CH:36]=[CH:35][C:34](B(O)O)=[CH:33]1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.CO.CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:27][C:10]([C:23]([F:25])([F:26])[F:24])([CH2:9][C:8]([C:6]1[CH:7]=[C:2]([C:34]2[CH:35]=[CH:36][S:32][CH:33]=2)[CH:3]=[CH:4][C:5]=1[O:30][CH3:31])([CH3:28])[CH3:29])[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 10340Sodium CarbonateHCID 581760Thiophene-3-boronic acidHCID 578097571-[4-(5-bromo-2-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethylpentyl]-1H-quinolin-4-one

Product 1

HCID 578098941-[2-hydroxy-4-(2-methoxy-5-thiophen-3-ylphenyl)-4-methyl-2-trifluoromethylpentyl]-1H-quinolin-4-oneYield 30%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 86594022DME MeOH DMFSolvent

Procedure

A mixture of 1-[4-(5-bromo-2-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethylpentyl]-1H-quinolin-4-one (0.2 g, 0.4 mmol), 3-thiopheneboronic acid (77 mg, 0.6 mmol), sodium carbonate (Na2CO3; 85 mg, 0.8 mmol) in DME-MeOH-DMF (1:1.5:0.5; 3.0 mL) was stirred for 10 minutes and Pd(PPh3)4 (46.2 mg, 0.04 mmol) was added. The mixture was microwaved for 15 minutes at 120° C., cooled to room temperature, and filtered through CELITE® filter aid. The residue was diluted with EtOAc (20 mL) and washed with aqueous NaOH (1.0M, 10 mL), water, and brine, and dried over sodium sulfate, and the volatiles removed in vacuo. The residue was purified by silica gel chromatography and then by reverse phase HPLC to yield 60 mg (30%) of 1-[2-hydroxy-4-(2-methoxy-5-thiophen-3-ylphenyl)-4-methyl-2-trifluoromethylpentyl]-1H-quinolin-4-one as a white foam.

Workup

  1. customThe mixture was microwaved for 15 minutes at 120° C.
  2. filtrationfiltered through CELITE®
  3. filtrationfilter aid
  4. additionThe residue was diluted with EtOAc (20 mL)
  5. washwashed with aqueous NaOH (1.0M, 10 mL), water, and brine
  6. dry with materialdried over sodium sulfate
  7. customthe volatiles removed in vacuo
  8. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-333acb9e3e7541029189eb630f86f767
Source dataset
uspto-grants-2009_08
Patent number
US07579469B2

Reaction notes

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