Water → HCID 67607650, compound

HRID 240209Notes

Reaction equation

HRID 240209 reaction equation
[C:1]([O:4][C:5]1[C:14]2[C:9](=[CH:10][C:11]([O:15][CH3:16])=[CH:12][CH:13]=2)[C:8]([C:17]2[CH:22]=[CH:21][C:20](Br)=[CH:19][CH:18]=2)=[C:7]([C:24]([O:26][CH3:27])=[O:25])[CH:6]=1)(=[O:3])[CH3:2].[CH3:28][O:29][C:30]1[CH:35]=[C:34]([O:36][CH3:37])[CH:33]=[CH:32][C:31]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].O>COCCOC>[C:1]([O:4][C:5]1[C:14]2[C:9](=[CH:10][C:11]([O:15][CH3:16])=[CH:12][CH:13]=2)[C:8]([C:17]2[CH:22]=[CH:21][C:20]([C:33]3[CH:32]=[CH:31][C:30]([O:29][CH3:28])=[CH:35][C:34]=3[O:36][CH3:37])=[CH:19][CH:18]=2)=[C:7]([C:24]([O:26][CH3:27])=[O:25])[CH:6]=1)(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 27343412,4-Dimethoxybenzeneboronic acidHCID 67607157HCID 67607157, compound

Product 1

HCID 67607650HCID 67607650, compoundYield 89.6%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

In an oven-dried flask placed under a nitrogen atmosphere, the product of Step 3 (25 g), 2,4-dimethoxyphenylboronic acid (11.1 g) and sodium carbonate (14.2 g) were stirred in 1,2-dimethoxyethane (125 mL) and deionized water (40 mL). A nitrogen purge line was inserted directly into the reaction mixture for 10 minutes and then removed. Tetrakis(triphenylphosphine)palladium(0) (1.4 g) was added to the reaction mixture. It was heated to reflux for 4 hours. After cooling to room temperature, the reaction mixture was poured into a beaker containing deionized water (1 L) and ice. Concentrated hydrochloric acid was added while stirring vigorously until the pH reached 3. The mixture was transferred to a separatory funnel and extracted with chloroform 3 times (400 mL each time). The organic layers were recovered, combined and then placed directly onto a silica gel column (600 g) eluting with a mixture of 30% ethyl acetate/70% hexanes. Fractions containing product were combined and concentrated by rotary evaporation. The resulting residue was slurried in a minimal amount of a solution of 10% ethyl acetate/90% hexanes. A solid precipitate was collected by vacuum filtration. 25.4 grams of methyl 4-acetoxy-1-(2′,4′-dimethoxy-[1,1′-biphenyl]-4-yl)-7-methoxy-2-naphthoate was isolated.

Workup

  1. customIn an oven-dried flask placed under a nitrogen atmosphere
  2. customA nitrogen purge line
  3. customremoved
  4. additionTetrakis(triphenylphosphine)palladium(0) (1.4 g) was added to the reaction mixture
  5. temperatureIt was heated
  6. temperatureto reflux for 4 hours
  7. additionthe reaction mixture was poured into a beaker
  8. additioncontaining deionized water (1 L) and ice
  9. additionConcentrated hydrochloric acid was added
  10. customThe mixture was transferred to a separatory funnel
  11. extractionextracted with chloroform 3 times (400 mL each time)
  12. customThe organic layers were recovered
  13. washeluting with a mixture of 30% ethyl acetate/70% hexanes
  14. additionFractions containing product
  15. concentrationconcentrated by rotary evaporation
  16. filtrationA solid precipitate was collected by vacuum filtration

Sources & evidence

ORD record
ord-423784fc16e943208d3c81cbecb508a9
Source dataset
uspto-grants-2014_02
Patent number
US08647538B2

Reaction notes

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