反应详情

To the solution of 2,2,2-trifluoro-N-(trans-2-phenylcyclopropyl)-N-(piperidin-4-ylmethyl)acetamide (60 mg, 0.184 mmol) (Example 11b) in chloroform (2 mL) was added isocyanatobenzene (0.030 mL, 0.276 mmol) The reaction mixture was stirred at room temperature for 1 hr. The saturated solution of NH4Cl was added, and layers were separated. The organic layer was evaporated and the oil dissolved in ethanol (2 mL) and 0.5 mL of 1 M NaOH was added. The reaction mixture was stirred for 1 hour at room temperature and then it was evaporated. The oil was purified on preparative HPLC (5 to 70% AcCN: H2O gradient with 0.1% formic acid modifier). The fractions were collected. The combined fractions were neutralized with aq. NH4OH, concentrated and extracted with ethyl acetate. The organic layer was washed with brine, dried over MgSO4 and evaporated. N-phenyl-4-(((trans-2-phenylcyclopropyl)amino)methyl)piperidine-1-carboxamide (54 mg, 0.147 mmol, 80% yield) was isolated as yellow oil. 1H NMR (400 MHz, METHANOL-d4) δ 7.32-7.38 (m, 2H), 7.20-7.31 (m, 4H), 7.10-7.17 (m, 1H), 7.05-7.10 (m, 2H), 6.98-7.05 (m, 1H), 4.20 (d, J=12.63 Hz, 2H), 2.79-3.01 (m, 2H), 2.65 (d, J=6.57 Hz, 2H), 2.28-2.45 (m, 1H), 1.95 (ddd, J=3.16, 5.94, 9.35 Hz, 1H), 1.70-1.90 (m, 3H), 1.14-1.31 (m, 2H), 1.10 (dt, J=4.86, 9.47 Hz, 1H), 1.03 (dt, 1H); LC-MS Rt=0.56 min; MS (ESI): 350.3 [M+H]+.

1. customlayers were separated
2. customThe organic layer was evaporated
3. dissolutionthe oil dissolved in ethanol (2 mL)
4. addition0.5 mL of 1 M NaOH was added
5. stirringThe reaction mixture was stirred for 1 hour at room temperature
6. customit was evaporated
7. customThe oil was purified on preparative HPLC (5 to 70% AcCN: H2O gradient with 0.1% formic acid modifier)
8. customThe fractions were collected
9. concentrationconcentrated
10. extractionextracted with ethyl acetate
11. washThe organic layer was washed with brine
12. dry with materialdried over MgSO4
13. customevaporated