Reacción #1546902

Ecuación de reacción

Water

N-tert-Butyloxycarbonyl-4-piperidone

2-phenylpiperidine

sodium cyanoborohydride

→

1-tert-Butyloxycarbonyl-4-[2-phenylpiperidin-1-yl]piperidine

Rendimiento 3.0%

Disolventes

ethyl acetate

methanol

Condiciones de reacción

Tratamiento posterior

1. 1
   Otroto give a granular precipitate which
2. 2
   Otrowas removed by filtration through celite
3. 3
   OtroThe filtrate was partitioned between water-ethyl acetate
4. 4
   Otrothe organic phase separated
5. 5
   Secadodried (MgSO4)
6. 6
   Concentraciónconcentrated
7. 7
   workup.DISSOLUTIONThe residue was dissolved in ethyl acetate
8. 8
   Lavadowashed with a saturated aqueous solution of citric acid
9. 9
   Extracciónextracted into ethyl acetate
10. 10
    SecadoThe organic phase was dried (MgSO4)
11. 11
    Concentraciónconcentrated
12. 12
    OtroThe residue was chromatographed
13. 13
    Otroto afford a partially purified mixture, which
14. 14
    LavadoThe organic phase was washed with a saturated aqueous solution of citric acid
15. 15
    OtroThe aqueous phase was separated
16. 16
    Extracciónextracted with ethyl acetate
17. 17
    SecadoThe organic phase was dried (MgSO4)
18. 18
    Concentraciónconcentrated
19. 19
    Otroto give the product in 3% yield

Procedimiento

N-tert-Butyloxycarbonyl-4-piperidone (5 g), 2-phenylpiperidine (4.03 g) and titanium isopropoxide (8.9 ml) were stirred at room temperature under a nitrogen atmosphere for 3 h. The resulting orange solution was diluted with methanol (40 ml), treated with sodium cyanoborohydride (1.6 g), and stirred for 20 h. Water (50 ml) was added to give a granular precipitate which was removed by filtration through celite. The filtrate was partitioned between water-ethyl acetate, the organic phase separated, dried (MgSO4) and concentrated. The residue was dissolved in ethyl acetate and washed with a saturated aqueous solution of citric acid. The aqueous phase was basified to pH10 using 4N sodium hydroxide, and extracted into ethyl acetate. The organic phase was dried (MgSO4) and concentrated. The residue was chromatographed using ethyl acetate-petroleum ether (20:80 to 50:50) to afford a partially purified mixture, which was dissolved in ethyl acetate. The organic phase was washed with a saturated aqueous solution of citric acid. The aqueous phase was separated, basified to pH10 using 4N sodium hydroxide and extracted with ethyl acetate. The organic phase was dried (MgSO4) and concentrated to give the product in 3% yield. δH (250 MHz, CDCl3) 1.16-1.79 (19H, m), 2.21-2.29 (2H, m), 2.41-2.50 (2H, m), 2.90-3.04 (1H, m), 3.36-3.44 (1H, m), 3.92-4.10 (2H, m), 7.16-7.40 (5H, m).

Fuente