反应详情

温度

80 °C

To a solution of 2,2,2-trifluoro-N-(trans-2-phenylcyclopropyl)-N-(piperidin-4-ylmethyl)acetamide (200 mg, 0.613 mmol) in acetonitrile (10 mL) was added potassium carbonate (254 mg, 1.838 mmol) followed by 2-bromopropane (98 mg, 0.797 mmol). The reaction mixture was heated in a sealed tube at 80° C. for 4 hours. The reaction mixture was filtered and evaporated. The resulting oil was purified by preparatory HPLC (5 to 40% AcCN: H2O with 0.1% formic acid modifier). The fractions were collected. The solution was neutralized with 1 M NaOH, concentrated and extracted with ethyl acetate. The organic layer was separated, dried over MgSO4, filtered and evaporated. The oil was dissolved in 6 ml of EtOH and 3 ml of 1 M NaOH. The reaction mixture was stirred for 20 min, and then it was concentrated. The concentrated solution was then partitioned between 2 ml of water and 5 mL of EtOAc. The organic layer was separated and evaporated. The resulting oil was dissolved in 3 mL of acetonitrile. 0.5 mL of 4 M HCl in dioxane was added. 3 mL of diethylether was added and the formed solid product was filtered. trans-N-((1-Isopropylpiperidin-4-yl)methyl)-2-phenylcyclopropanamine (80 mg, 0.246 mmol, 40.1% yield) was isolated as white solid. 1H NMR (400 MHz, METHANOL-d4) δ 7.29-7.40 (m, 2H), 7.13-7.28 (m, 3H), 3.43-3.63 (m, 3H), 3.21 (d, J=6.57 Hz, 2H), 3.11 (t, 2H), 3.04 (dt, J=3.98, 7.71 Hz, 1H), 2.49-2.69 (m, 1H), 2.17 (d, J=12.63 Hz, 3H), 1.56-1.86 (m, 3H), 1.34-1.48 (m, 7H); LC-MS Rt=0.42 min; MS (ESI): 273.3 [M+H]+.

1. filtrationThe reaction mixture was filtered
2. customevaporated
3. customThe resulting oil was purified by preparatory HPLC (5 to 40% AcCN: H2O with 0.1% formic acid modifier)
4. customThe fractions were collected
5. concentrationconcentrated
6. extractionextracted with ethyl acetate
7. customThe organic layer was separated
8. dry with materialdried over MgSO4
9. filtrationfiltered
10. customevaporated
11. dissolutionThe oil was dissolved in 6 ml of EtOH
12. concentrationit was concentrated
13. customThe concentrated solution was then partitioned between 2 ml of water and 5 mL of EtOAc
14. customThe organic layer was separated
15. customevaporated
16. dissolutionThe resulting oil was dissolved in 3 mL of acetonitrile
17. addition0.5 mL of 4 M HCl in dioxane was added
18. addition3 mL of diethylether was added
19. filtrationthe formed solid product was filtered