Reaction #41853

Reaction equation

(S)-3-(4-Bromo-phenyl)-2-tert-butoxycarbonylamino-propionic acid methyl ester

4-cyanobenzeneboronic acid

Na2CO3

→

(S)-2-tert-Butoxycarbonylamino-3-(4′-cyano-biphenyl-4-yl)-propionic acid methyl ester

Yield 68.2%

Solvents

toluene

Conditions

Workup

1. 1
   TemperatureThe mixture was heated
2. 2
   Temperatureat reflux for 7 h
3. 3
   OtherAfter completion of the reaction
4. 4
   WashThe organic was washed with 10% Na2CO3 and 1 N HCl
5. 5
   DryingThe organic was dried over sodium sulfate
6. 6
   Concentrationconcentrated under reduced pressure
7. 7
   Otherto afford the crude product
8. 8
   OtherThe residue was purified by column chromatography (hexanes-EtOAc)

Procedure

Suzuki coupling: To a solution of (S)-3-(4-Bromo-phenyl)-2-tert-butoxycarbonylamino-propionic acid methyl ester (70.1 mmol) in toluene (250 mL) was added 4-cyanobenzeneboronic acid (105 mmol), Pd(PPh3)4 (3.5 mmol), and 1N Na2CO3 solution (105 mL). The mixture was heated at reflux for 7 h. After completion of the reaction, the aqueous layer was drained. The organic was washed with 10% Na2CO3 and 1 N HCl. The organic was dried over sodium sulfate and concentrated under reduced pressure to afford the crude product. The residue was purified by column chromatography (hexanes-EtOAc) to provide (S)-2-tert-Butoxycarbonylamino-3-(4′-cyano-biphenyl-4-yl)-propionic acid methyl ester (18.2 g). LC-MS (m/z) 382.

Source