Reaktion #61980

Reaktionsgleichung

sodium bicarbonate

product

4-(3-Chloro-propoxy)-benzaldehyde

1,2,3,4-tetrahydro-isoquinoline

sodium triacetoxyborohydride

piperidine

sodium carbonate

potassium iodide

→

title compound

2-[4-(3-Piperidin-1-yl-propoxy)-benzyl]-1,2,3,4-tetrahydro-isoquinoline

Lösungsmittel

n-butanol

water

DCE

acetic acid

Reaktionsbedingungen

Aufarbeitung

1. 1
   ExtraktionThe resulting mixture was extracted with DCM (3×10 mL)
2. 2
   TrocknenThe combined organic phases were dried (magnesium sulfate)
3. 3
   Sonstigeevaporated
4. 4
   Sonstigegiving a material which
5. 5
   workup.WAITAfter 16 h
6. 6
   Temperaturthe reaction was cooled to RT
7. 7
   Extraktionextracted with DCM (3×20 mL)
8. 8
   TrocknenThe combined organic phases were dried (magnesium sulfate)
9. 9
   Sonstigeevaporated
10. 10
    workup.ADDITIONThe residue was treated with ether (20 mL)
11. 11
    Filtrationfiltered
12. 12
    workup.ADDITIONThe filtrate was treated with hydrogen chloride (2.5 mL of a 2 M solution in ether)
13. 13
    Sonstigeevaporated
14. 14
    TrocknenThe residue was dried in vacuo, and ether
15. 15
    workup.ADDITIONwas added
16. 16
    Sonstigeto form
17. 17
    FiltrationFiltration

Vorschrift

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).

Quelle