반응 #9697

반응 방정식

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

수율 33.0%

용매

toluene

반응 조건

후처리

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

실험 절차

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).

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