Potassium Carbonate → 6-Fluoro-4-methoxy-biphenyl-3-carboxylic acid methyl ester

HRID 2229564Notes

Reaction equation

HRID 2229564 reaction equation
[CH3:1][O:2][C:3](=[O:14])[C:4]1[CH:9]=[C:8](Br)[C:7]([F:11])=[CH:6][C:5]=1[O:12][CH3:13].C([O-])([O-])=O.[K+].[K+].[C:21]1(B(O)O)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>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.OO>[CH3:1][O:2][C:3]([C:4]1[CH:9]=[C:8]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:7]([F:11])=[CH:6][C:5]=1[O:12][CH3:13])=[O:14]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 66827Phenylboronic AcidHCID 22093493Methyl 5-bromo-4-fluoro-2-methoxybenzoate

Product 1

HCID 220934916-Fluoro-4-methoxy-biphenyl-3-carboxylic acid methyl esterYield 91%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 784Hydrogen PeroxideSolvent

Conditions

Temperature
110 °C

Procedure

To a flame dried flask containing degassed toluene (15.2 mL, 0.5 M) was added 5-bromo-4-fluoro-2-methoxy-benzoic acid methyl ester (2.0 g, 7.6 mmol), anhydrous K2CO3 (2.1 g, 15.2 mmol), phenylboronic acid (3.7 g, 30.4 mmol), and Pd(PPh3)4 (0.88 g, 0.76 mmol). Using a reflux condenser, the stirring mixture was heated to 110° C. for 3.5 h. The mixture was then cooled to room temperature, placed in an ice bath and H2O2 (30%, 10 mL) was slowly added. The ice bath was removed and the reaction was allowed to stir at room temperature for one hour. The mixture was then diluted with ether and washed successively with 2 N HCl and saturated aq NaCl. The organic layer was dried over Na2SO4, filtered, and concentrated to afford a brown oil. Purification by MPLC (10-100% ethyl acetate in heptane, 23 mL/min, 75 min) provided 6-fluoro-4-methoxy-biphenyl-3-carboxylic acid methyl ester (1.8 g, 91%) as a pale yellow solid: Rf 0.5 (40% ethyl acetate in heptane); 1H NMR (CDCl3, 300 MHz) δ 8.00 (d, J=9.0 Hz, 1H), 7.53-7.33 (m, 5H), 6.79 (d, J=12.6 Hz, 1H), 3.94 (s, 3H), 3.89 (s, 3H).

Workup

  1. customTo a flame dried flask
  2. additioncontaining
  3. customdegassed toluene (15.2 mL, 0.5 M)
  4. temperatureThe mixture was then cooled to room temperature
  5. customplaced in an ice bath
  6. customThe ice bath was removed
  7. additionThe mixture was then diluted with ether
  8. washwashed successively with 2 N HCl and saturated aq NaCl
  9. dry with materialThe organic layer was dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customto afford a brown oil
  13. customPurification by MPLC (10-100% ethyl acetate in heptane, 23 mL/min, 75 min)

Sources & evidence

ORD record
ord-c0041167134c4def842a69cf1dc65c7c
Source dataset
uspto-grants-2002_07
Patent number
US06420426B1

Reaction notes

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