Sodium Carbonate → Methyl 2'-methoxy-2-methylbiphenyl-4-carboxylate

HRID 639264Notes

Reaction equation

HRID 639264 reaction equation
[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7](Br)=[C:6]([CH3:11])[CH:5]=1.[CH3:13][O:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:1][O:2][C:3]([C:4]1[CH:9]=[CH:8][C:7]([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[O:14][CH3:13])=[C:6]([CH3:11])[CH:5]=1)=[O:12]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27339582-Methoxyphenylboronic acidHCID 3294148Methyl 4-bromo-3-methylbenzoate

Product 1

HCID 67528780Methyl 2'-methoxy-2-methylbiphenyl-4-carboxylateYield 89.7%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 3-methyl-4-bromobenzoic acid methyl ester (2.0 g, 8.7 mmol), 2-methoxyphenyl boronic acid (1.32 g, 8.7 mmol) and sodium carbonate (4.1 g, 38.7 mmol) in toluene:ethanol:water (50 mL:25 mL: 25 mL) was purged with nitrogen for 1 hour. After addition of the tetrakis(triphenylphosphine) palladium(0) catalyst (0.50 g, 0.43 mmol), the reaction mixture was heated at 100° C. overnight. After cooling, the reaction was filtered through Celite® and the cake washed with ethyl acetate. The organic layer was washed with water, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give a brown oil. Purification by flash chromatography on silica gel with a solvent gradient from 20% to 50% dichloromethane in hexane gave 2.0 g of product as a colorless oil. MS [(+)APCI, m/z]: 257 [M+H]+. Anal. Calcd. for C16H16O3: C, 74.98; H, 6.29. Found: C, 74.06; H, 6.17.

Workup

  1. customethanol:water (50 mL:25 mL: 25 mL) was purged with nitrogen for 1 hour
  2. temperatureAfter cooling
  3. filtrationthe reaction was filtered through Celite®
  4. washthe cake washed with ethyl acetate
  5. washThe organic layer was washed with water
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give a brown oil
  10. customPurification by flash chromatography on silica gel with a solvent gradient from 20% to 50% dichloromethane in hexane

Sources & evidence

ORD record
ord-3710234cd3994c39b667c9f4a79f4a78
Source dataset
uspto-grants-2010_04
Patent number
US07691848B2

Reaction notes

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