Reacción #360040

Ecuación de reacción

HCl

LiAlH4

4-[4-(3-pyrrolidin-1-yl-propoxy)-phenyl]-tetrahydro-pyran-4-carbonitrile

Sodium hydroxide

→

title compound

Rendimiento 81.0%

{4-[4-(3-Pyrrolidin-1-ylpropoxy)phenyl]tetrahydropyran-4-yl}methylamine dihydrochloride

Rendimiento 81.0%

Disolventes

dioxane

dioxane

Et2O DCM

Et2O DCM

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturato warm up to ambient temperature
2. 2
   Filtraciónthe resulting solids were filtered
3. 3
   Lavadowashed with Et2O/DCM (1:1, 6×50 mL)
4. 4
   Concentraciónconcentrated in vacuo at 40° C
5. 5
   OtroA portion of the crude product from the above reaction (0.5 g, 1.57 mmol)
6. 6
   workup.STIRRINGThe reaction was stirred for 3 hours
7. 7
   Filtraciónfiltered under a blanket of N2 (hygroscopic)
8. 8
   Lavadowashed with TBME
9. 9
   Otrodried in the oven at 40° C.

Procedimiento

To a stirred suspension of LiAlH4 (1.81 g, 47.7 mmol, 5 eq) in Et2O/DCM (1:1, 30 mL) at 0 to 5° C. under a nitrogen atmosphere was added 4-[4-(3-pyrrolidin-1-yl-propoxy)-phenyl]-tetrahydro-pyran-4-carbonitrile (3 g, 9.55 mmol) in Et2O/DCM (1:1, 30 mL) over 15 minutes maintaining the temperature at 5 to 10° C. The reaction mixture was allowed to warm up to ambient temperature and stirred until complete. Sodium hydroxide (2N, 15 mL) was added dropwise and the resulting solids were filtered, washed with Et2O/DCM (1:1, 6×50 mL) and concentrated in vacuo at 40° C. A portion of the crude product from the above reaction (0.5 g, 1.57 mmol) was dissolved in dioxane (5 mL) and 4M HCl in dioxane (1.18 mL) added under N2. The reaction was stirred for 3 hours and filtered under a blanket of N2 (hygroscopic), washed with TBME and dried in the oven at 40° C. to give the title compound as a white solid (0.5 g, 81%). 1H NMR (400 MHz, DMSO-d6) δ11.24 (br s, 1H), 8.00 (br s, 3H), 7.33 (d, 2H), 6.98 (d, 2H), 4.08 (t, 2H), 3.76-3.63 (m, 2H), 3.60-3.46 (m, 2H), 3.45-3.18 (m, 4H), 3.07-2.87 (m, 4H), 2.25-1.77 (m, 10H).

Fuente