反应详情

Into a solution of tert-butyl-4-[3-({3-[4-(3,4-difluorophenoxy)phenyl]propanoyl}amino)-4-fluorophenyl]-1-piperidinecarboxylate (85.0 mg, 0.150 mmol) in CH2Cl2 (2.0 mL) was added trifluoroacetic acid (170 mg, 1.50 mmol) at room temperature. The reaction mixture was stirred for 10 min and concentrated in vacuo. The residue was dissolved in CHCl3/i-PrOH (3:1, 10 mL) and was basified to pH 11 with 5% KOH solution. The organic layer was extracted and the aqueous layer was extracted with CHCl3/i-PrOH (3:1, 3×10 mL). The combined organic extracts were washed with brine, dried over MgSO4, filtered and concentrated in vacuo to afford 3-[4-(3,4-difluorophenoxy)phenyl]-N-[2-fluoro-5-(4-piperidinyl)phenyl]propanamide (65.0 mg, 92%): 1H NMR (400 MHz, CD3OD) δ 8.27-8.12 (m, 1H), 7.39 (s, 1H), 7.33-7.17 (m, 2H), 7.17-7.06 (m, 1H), 7.06-6.97 (m, 1H), 6.97-6.87 (m, 3H), 6.86-6.74 (m, 1H), 6.74-6.62 (m, 1H), 6.15-5.63 (br, 1H), 3.55-3.31 (m, 2H), 3.15-2.97 (m, 2H), 2.97-2.79 (m, 2H), 2.79-2.59 (m, 3H), 2.05-1.79 (m, 4H); ESMS m/e: 455.2 (M+H)+.

1. concentrationconcentrated in vacuo
2. dissolutionThe residue was dissolved in CHCl3/i-PrOH (3:1, 10 mL)
3. extractionThe organic layer was extracted
4. extractionthe aqueous layer was extracted with CHCl3/i-PrOH (3:1, 3×10 mL)
5. washThe combined organic extracts were washed with brine
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated in vacuo