Reaction #6694

Reaction equation

2,3-difluoro-4-(4-pentyloxybutoxy)phenylboronic acid

2,3-Difluoro4-(4-pentyloxybutoxy)phenylboronic acid

4-bromo-benzoic acid ethyl ester

4-Benzyloxybenzoic acid

sodium carbonate

→

2′,3′-difluoro-4′-(4-pentyloxybutoxy)-biphenyl-4-carboxylic acid ethyl ester

Yield 88.0%

2′,3′-Difluoro-4′-(4-pentyloxybutoxy)-biphenyl-4-carboxylic acid ethyl ester

Yield 88.0%

Solvents

water toluene

Conditions

Workup

1. 1
   Extractionextracted with ethyl acetate:hexane(1:1)
2. 2
   Washwashed with brine
3. 3
   Dryingdried over MgSO4
4. 4
   Concentrationconcentrated in vacuo
5. 5
   OtherThe purification by chromatography
6. 6
   Otheron silica gel (5% EtOAc/hexanes) and recrystallization from acetonitrile

Procedure

A biphasic solution of 2,3-difluoro-4-(4-pentyloxybutoxy)phenylboronic acid (25) (1 equi.), 4-bromo-benzoic acid ethyl ester (12), (1 equi.), sodium carbonate (2.7 equi.), and tetrakis(triphenylphoshine)palladium catalyst (0.01 equi.) in water-toluene (1:1) (2 mL/mmole) was stirred at 100 C. temperature for 12 h., cooled to room temperature, extracted with ethyl acetate:hexane(1:1), washed with brine, dried over MgSO4, and concentrated in vacuo. The purification by chromatography on silica gel (5% EtOAc/hexanes) and recrystallization from acetonitrile afforded 2′,3′-difluoro-4′-(4-pentyloxybutoxy)-biphenyl-4-carboxylic acid ethyl ester (26) as a white solid (88%).

Source