Reaktion #159325

Reaktionsgleichung

(R)-4-(pyrrolidin-3-ylamino)benzonitrile dihydrochloride

pyridine

tert-butyl 3-amino-8-azabicyclo[3.2.1]octane-8-carboxylate

triphosgene

NaHCO3

→

tert-butyl 3-((R)-3-(5-cyanopyridin-2-ylamino)pyrrolidine-1-carboxamido)-8-azabicyclo[3.2.1]octane-8-carboxylate

Ausbeute 18.0%

Lösungsmittel

CH2Cl2

CH2Cl2

EtOAc

CH2Cl2

brine

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe organic layer was separated
2. 2
   Waschenwashed with 5% aq HCl (20 mL)
3. 3
   Trocknendried over Na2SO4
4. 4
   SonstigeRemoval of the solvent
5. 5
   workup.WAITleft an oil (246 mg) which
6. 6
   Sonstigewas purified by prep HPLC

Vorschrift

To a stirred, ice-cold mixture of tert-butyl 3-amino-8-azabicyclo[3.2.1]octane-8-carboxylate (149 mg, 0.66 mmol), CH2Cl2 (4 mL) and satd aq NaHCO3 (2 mL) was added solid triphosgene (65 mg, 0.22 mmol). The mixture was stirred in the ice bath for 30 min and diluted with CH2Cl2 (6 mL) and brine (8 mL). The organic layer was separated and added to a stirred solution of (R)-4-(pyrrolidin-3-ylamino)benzonitrile dihydrochloride (165 mg, 0.66 mmol) in CH2Cl2 (2 mL) and dry pyridine (0.5 mL). The mixture was stirred overnight at rt, diluted with EtOAc (90 mL), washed with 5% aq HCl (20 mL), satd aq NaHCO3 (20 mL) and brine (20 mL), and dried over Na2SO4. Removal of the solvent left an oil (246 mg) which was purified by prep HPLC to afford tert-butyl 3-((R)-3-(5-cyanopyridin-2-ylamino)pyrrolidine-1-carboxamido)-8-azabicyclo[3.2.1]octane-8-carboxylate (49 mg, 18%). LC-MS Method 1 tR=1.52 min, m/z=441, 385.

Quelle