Potassium Fluoride → 3-{4-[1-(4'-Isopropyl-2-methyl-biphenyl-4-yl)-5-methyl-hexyloxy]-benzoylamino}-propionic acid methyl ester

HRID 1669331Notes

Reaction equation

HRID 1669331 reaction equation
[CH3:1][O:2][C:3](=[O:31])[CH2:4][CH2:5][NH:6][C:7](=[O:30])[C:8]1[CH:13]=[CH:12][C:11]([O:14][CH:15]([C:22]2[CH:27]=[CH:26][C:25](Br)=[C:24]([CH3:29])[CH:23]=2)[CH2:16][CH2:17][CH2:18][CH:19]([CH3:21])[CH3:20])=[CH:10][CH:9]=1.[CH:32]([C:35]1[CH:40]=[CH:39][C:38](B(O)O)=[CH:37][CH:36]=1)([CH3:34])[CH3:33].[F-].[K+]>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3](=[O:31])[CH2:4][CH2:5][NH:6][C:7](=[O:30])[C:8]1[CH:13]=[CH:12][C:11]([O:14][CH:15]([C:22]2[CH:27]=[CH:26][C:25]([C:38]3[CH:39]=[CH:40][C:35]([CH:32]([CH3:34])[CH3:33])=[CH:36][CH:37]=3)=[C:24]([CH3:29])[CH:23]=2)[CH2:16][CH2:17][CH2:18][CH:19]([CH3:21])[CH3:20])=[CH:10][CH:9]=1

Participants

5

Reactant 3

HCID 522689Potassium FluorideHCID 27734804-Isopropylphenylboronic acidHCID 673419823-{4-[1-(4-Bromo-3-methyl-phenyl)-5-methyl-hexyloxy]-benzoylamino}-propionic acid methyl ester

Product 1

HCID 673432783-{4-[1-(4'-Isopropyl-2-methyl-biphenyl-4-yl)-5-methyl-hexyloxy]-benzoylamino}-propionic acid methyl ester

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

3-{4-[1-(4-Bromo-3-methyl-phenyl)-5-methyl-hexyloxy]-benzoylamino}-propionic acid methyl ester (460 mg, 0.940 mmol) was dissolved in toluene (2.5 mL), followed by palladium tetrakis triphenylphosphine (46 mg, 0.0395 mmol), 4-isopropyl-phenyl boronic acid (308 mg, 1.88 mmol), and potassium fluoride (109 mg, 1.88 mmol). The reaction was purged with nitrogen and heated to reflux, then the water (2.5 mL) was added. The reaction was monitored by HPLC, and upon completion, allowed to cool to room temperature. The reaction was diluted with EtOAc and then celite added, followed by water. This mixture was then filtered through a pad of celite. The solution was separated in a separatory funnel, then the organic layer was washed with 0.1N sodium hydroxide, water, and brine. The organic layer was dried over anhydrous sodium sulfate, then concentrated. The product was purified by flash column chromatography (444 mg, 0.800 mmol).

Workup

  1. customThe reaction was purged with nitrogen
  2. temperatureheated
  3. temperatureto reflux
  4. additionthe water (2.5 mL) was added
  5. additionThe reaction was diluted with EtOAc
  6. additioncelite added
  7. filtrationThis mixture was then filtered through a pad of celite
  8. customThe solution was separated in a separatory funnel
  9. washthe organic layer was washed with 0.1N sodium hydroxide, water, and brine
  10. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  11. concentrationconcentrated
  12. customThe product was purified by flash column chromatography (444 mg, 0.800 mmol)

Sources & evidence

ORD record
ord-9f765b8b6d2c49abb0862b0147671bf9
Source dataset
uspto-grants-2011_08
Patent number
US07989457B2

Reaction notes

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