反应详情

温度

105 °C

A solution of the product of Example 11 (1.0 g), 1,2,3,4-tetrahydro-isoquinoline (0.0.69 mL), and acetic acid (0.29 mL) in DCE (10 mL) was treated with sodium triacetoxyborohydride (1.5 g). After 16 h, saturated aqueous sodium bicarbonate was added. The resulting mixture was extracted with DCM (3×10 mL). The combined organic phases were dried (magnesium sulfate) and evaporated, giving a material which was dissolved in n-butanol (20 mL), treated with piperidine (0.65 mL), sodium carbonate (800 mg), and potassium iodide (42 mg), and heated to 105° C. After 16 h, the reaction was cooled to RT, treated with water (10 mL), and extracted with DCM (3×20 mL). The combined organic phases were dried (magnesium sulfate) and evaporated. The residue was treated with ether (20 mL), and filtered. The filtrate was treated with hydrogen chloride (2.5 mL of a 2 M solution in ether) followed by methanol (3 mL). The resulting solution was stirred for 1 h, and evaporated. The residue was dried in vacuo, and ether was added, followed by enough methanol to cause a precipitate to form. Filtration gave the title compound as an amorphous pink powder (0.86 g). 1H NMR (400 MHz, CDCl3): 7.27 (d, J=8.6 Hz, 2H), 7.13-7.05 (m, 4H), 6.99-6.96 (m, 1H), 6.89-6.83 (m, 2H), 4.00 (t, J=6.3 Hz, 2H), 3.60 (s, 4H), 2.89 (t, J=5.7 Hz, 2H), 2.72 (t, J=5.8 Hz, 2H), 2.53-2.37 (m, 6H), 2.03-1.95 (m, 2H), 1.64-1.57 (m, 4H), 1.49-1.40 (m, 2H).

1. extractionThe resulting mixture was extracted with DCM (3×10 mL)
2. dry with materialThe combined organic phases were dried (magnesium sulfate)
3. customevaporated
4. customgiving a material which
5. waitAfter 16 h
6. temperaturethe reaction was cooled to RT
7. extractionextracted with DCM (3×20 mL)
8. dry with materialThe combined organic phases were dried (magnesium sulfate)
9. customevaporated
10. additionThe residue was treated with ether (20 mL)
11. filtrationfiltered
12. additionThe filtrate was treated with hydrogen chloride (2.5 mL of a 2 M solution in ether)
13. customevaporated
14. dry with materialThe residue was dried in vacuo, and ether
15. additionwas added
16. customto form
17. filtrationFiltration