Reaction #9644

Reaction equation

Na2CO3

Methyl trans-2-(4-bromobenzoyl)cyclopentanecarboxylate

4-aminophenyl boronic acid

dichloromethane

→

methyl trans-2-[(4′-amino-1,1′-biphenyl-4-yl)carbonyl]-cyclopentanecarboxylate

Yield 67.4%

Solvents

EtOAc

EtOH

Toluene

Conditions

Workup

1. 1
   Otherresulting solution
2. 2
   Otherwas degassed for 30 minutes
3. 3
   TemperatureThe mixture was cooled to it
4. 4
   OtherThe solvent was removed by rotary evaporation
5. 5
   workup.ADDITIONWater and EtOAc were added
6. 6
   Extractionthe aqueous layer was extracted with EtOAc
7. 7
   WashThe combined organic phases were washed with water, brine
8. 8
   Dryingdried over anhydrous sodium sulfate
9. 9
   Filtrationfiltered
10. 10
    Concentrationconcentrated in vacuo
11. 11
    OtherThe residue was purified by flash chromatography (Biotage Flash 40M)

Procedure

Methyl trans-2-(4-bromobenzoyl)cyclopentanecarboxylate (1.60 g, 5.14 mmol) and 4-aminophenyl boronic acid (1.07 g, 6.17 mmol) were combined in a dry flask under argon. Toluene (25 mL), EtOH (10 mL), and 3 M aqueous Na2CO3 (8.50 mL, 25 mmol) were added and resulting solution was degassed for 30 minutes by using a flow of argon. Then [1,1′-bis(diphenylphosphino)-ferrocene]dichloro palladium(II), 1:1 complex with dichloromethane (419.9 mg, 0.51 mmol), was added and the resulting mixture was heated at 85° C. for 16 h. The mixture was cooled to it, diluted with EtOAc, and passed through a Celite® pad. The solvent was removed by rotary evaporation. Water and EtOAc were added and the aqueous layer was extracted with EtOAc. The combined organic phases were washed with water, brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by flash chromatography (Biotage Flash 40M) using 29 to 33% ethyl acetate in hexane to afford methyl trans-2-[(4′-amino-1,1′-biphenyl-4-yl)carbonyl]-cyclopentanecarboxylate (1.12 g, 67%). 1H NMR (400 MHz, CD2Cl2) δ 1.71–1.97 (m, 4H), 2.17 (m, 2H), 3.44 (m, 1H), 3.65 (s, 3H), 4.12 (m, 1H), 6.84 (m, 2H), 7.51 (m, 2H), 7.66 (m, 2H), 8.00 (m, 2H).

Source