تفاعل #360040

معادلة التفاعل

HCl

LiAlH4

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

Sodium hydroxide

→

title compound

المردود 81.0%

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

المردود 81.0%

المذيبات

dioxane

dioxane

Et2O DCM

Et2O DCM

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةto warm up to ambient temperature
2. 2
   ترشيحthe resulting solids were filtered
3. 3
   غسيلwashed with Et2O/DCM (1:1, 6×50 mL)
4. 4
   تركيزconcentrated in vacuo at 40° C
5. 5
   أخرىA 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
   ترشيحfiltered under a blanket of N2 (hygroscopic)
8. 8
   غسيلwashed with TBME
9. 9
   أخرىdried in the oven at 40° C.

الإجراء التجريبي

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).

المصدر