Water → HCID 67957761, compound

HRID 571556Notes

Reaction equation

HRID 571556 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].[C:28]1(B(O)O)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C(=O)([O-])[O-].[Na+].[Na+].O>COCCOC>[C:20]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH:21]=[CH:22][C:17]([C:8]2[C:9]3[C:14](=[CH:13][CH:12]=[C:11]([O:15][CH3:16])[CH:10]=3)[C:5]([O:4][C:1](=[O:3])[CH3:2])=[CH:6][C:7]=2[C:24]([O:26][CH3:27])=[O:25])=[CH:18][CH:19]=1

Participants

6

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 67607157HCID 67607157, compound

Product 1

HCID 67957761HCID 67957761, compoundYield 100%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

In an oven-dried placed flask under a nitrogen atmosphere, the product of Step 3 (150 g), phenylboronic acid (45 g) and sodium carbonate (85 g) were stirred in 1,2-dimethoxyethane (750 mL) and deionized water (225 mL). A nitrogen purge line was inserted directly into the reaction mixture for 10 minutes. Tetrakis(triphenylphosphine)palladium(0) (10 g) was added and the reaction mixture heated to reflux for 4.5 hours. After cooling to room temperature, the reaction mixture was slowly poured into a beaker containing deionized water (1.5 L) and ice while stirring. Concentrated hydrochloric acid was added until the pH reached 3. A separatory funnel was used to perform chloroform extractions (3×600 mL). The recovered organic layers were combined, washed with a saturated aqueous solution of sodium bicarbonate, dried over sodium sulfate and concentrated by rotary evaporation. The resulting residue was purified by column chromatography on silica gel (400 g) eluting with a solution of 30% ethyl acetate/70% hexanes. Fractions containing product were combined and concentrated by rotary evaporation yielding methyl 1-([1,1′-biphenyl]-4-yl)-4-acetoxy-7-methoxy-2-naphthoate (149 g).

Workup

  1. customA nitrogen purge line
  2. additionTetrakis(triphenylphosphine)palladium(0) (10 g) was added
  3. temperaturethe reaction mixture heated
  4. temperatureto reflux for 4.5 hours
  5. additionthe reaction mixture was slowly poured into a beaker
  6. additioncontaining deionized water (1.5 L) and ice
  7. additionConcentrated hydrochloric acid was added until the pH
  8. customA separatory funnel was used
  9. extractionchloroform extractions (3×600 mL)
  10. washwashed with a saturated aqueous solution of sodium bicarbonate
  11. dry with materialdried over sodium sulfate
  12. concentrationconcentrated by rotary evaporation
  13. customThe resulting residue was purified by column chromatography on silica gel (400 g)
  14. washeluting with a solution of 30% ethyl acetate/70% hexanes
  15. additionFractions containing product
  16. concentrationconcentrated by rotary evaporation

Sources & evidence

ORD record
ord-327948c1316744509c65fe4082ce898a
Source dataset
uspto-grants-2015_05
Patent number
US09028728B2

Reaction notes

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