Reaction #51654

Reaction equation

4-fluorophenyl boronic acid

methyl 4-hydroxybenzoate

→

4-(4-fluorophenoxy)benzoic acid

Yield 91.9%

Solvents

CH2Cl2

Conditions

Workup

1. 1
   Otherbubbling through it
2. 2
   workup.ADDITIONThe reaction mixture is diluted with CH2Cl2
3. 3
   Filtrationfiltered through silica gel
4. 4
   WashThe silica gel is washed with EtOAc-heptane
5. 5
   ConcentrationThe solution is concentrated in vacuo
6. 6
   workup.DISSOLUTIONdissolved in dioxane (15 mL)
7. 7
   workup.ADDITIONTo this solution is added aqueous LiOH (1N, 15 mL)
8. 8
   workup.STIRRINGstirred for 18 hours at room temperature
9. 9
   workup.ADDITIONTo this reaction mixture is added aqueous HCl (1N) until acidic,
10. 10
    FiltrationThe resulting precipitate is collected by filtration
11. 11
    Washrinsed with water
12. 12
    Otherdried in vacuo

Procedure

To a flask with 4-fluorophenyl boronic acid (2.1 g, 15 mmol), copper(II) acetate (1.4 g, 7.5 mmol), activated powdered molecular sieves (approximately 2 g), and methyl 4-hydroxybenzoate (1.2 g, 7.5 mmol) is added TEA (5.2 mL, 38 mmol) followed by CH2Cl2 (75 mL). The reaction is stirred for 16 hours at room temperature with air bubbling through it. The reaction mixture is diluted with CH2Cl2 and filtered through silica gel. The silica gel is washed with EtOAc-heptane. The solution is concentrated in vacuo and dissolved in dioxane (15 mL). To this solution is added aqueous LiOH (1N, 15 mL) and stirred for 18 hours at room temperature. To this reaction mixture is added aqueous HCl (1N) until acidic, having a pH less than 6. The resulting precipitate is collected by filtration and rinsed with water, and dried in vacuo to give 4-(4-fluorophenoxy)benzoic acid (1.6 g, 90%). MS for C13H9FO3 (ESI) (M−H)− m/z 231.

Source