Reaktion #9697

Reaktionsgleichung

ethyl 4-(4′-amino-1,1′-biphenyl-4-yl)-4-oxo-2-(2-phenylethyl)butanoate

2-chlorobenzoxazole

sodium hydroxide

→

4-[4′-(1,3-benzoxazol-2-ylamino)-1,1′-biphenyl-4-yl]4-oxo-2-(2-phenylethyl)butanoic acid

Ausbeute 33.0%

Lösungsmittel

toluene

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturat reflux for 16 h
2. 2
   SonstigeSolvent was removed under reduced pressure
3. 3
   workup.DISSOLUTIONthe residue was dissolved in dichloromethane
4. 4
   WaschenThe solution was washed with water, solvent
5. 5
   Sonstigewas again removed under reduced pressure
6. 6
   workup.DISSOLUTIONthe residue was dissolved in methanol (1 mL)
7. 7
   Einengenconcentrated under reduced pressure
8. 8
   SonstigeThe residue was purified by preparative reverse-phase HPLC (water/acetonitrile gradient, containing 0.1% TFA)

Vorschrift

A solution of ethyl 4-(4′-amino-1,1′-biphenyl-4-yl)-4-oxo-2-(2-phenylethyl)butanoate (100 mg, 0.25 mmol) and 2-chlorobenzoxazole (38.3 mg, 0.25 mmol) in toluene (1.0 mL) was heated at reflux for 16 h. Solvent was removed under reduced pressure, and the residue was dissolved in dichloromethane. The solution was washed with water, solvent was again removed under reduced pressure, and the residue was dissolved in methanol (1 mL) and tetrahydrofuran (1 mL). A 1 N aqueous solution of sodium hydroxide (0.77 mL, 0.77 mmol) was added, and the mixture was stirred at rt for 16 h and then concentrated under reduced pressure. The residue was purified by preparative reverse-phase HPLC (water/acetonitrile gradient, containing 0.1% TFA) to afford 4-[4′-(1,3-benzoxazol-2-ylamino)-1,1′-biphenyl-4-yl]4-oxo-2-(2-phenylethyl)butanoic acid (40 mg, 33% yield). LC-MS ret. time 4.14 min, m/z 519.5 (MH+); 1H NMR (300 MHz, DMSO-d6) δ 1.82–1.90 (m, 2H), 2.68 (m, 2H), 2.80–2.85 (m, 1H), 3.16 (dd, 1H), 3.41 (m, 1H), 7.10–7.30 (m, 8H), 7.48 (t, 2H), 7.78–7.86 (m, 4H), 7.89 (d, 2H), 8.02 (d, 2H), 10.83 (br s, 1H).

Quelle