Reaktion #164158

Reaktionsgleichung

HCl dioxane

2-(tert-butoxycarbonylamino)-2-phenylacetic acid

HOBt

DCC

3(R)-quinuclidinol

di hydrochloride

(R)-quinuclidin-3-yl 2-(tert-butoxycarbonylamino)-2-phenylacetate

→

(R)-quinuclidin-3-yl 2-amino-2-phenylacetate di-hydrochloride

Ausbeute 97.0%

Lösungsmittel

THF

DCM

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe solvent is removed under reduced pressure
2. 2
   Waschenwashed twice with 2M K2CO3
3. 3
   TrocknenThe organic phase is dried over Na2SO4
4. 4
   Filtrationfiltered
5. 5
   Sonstigeevaporated to dryness
6. 6
   SonstigeThe compound is triturated with hexane
7. 7
   Sonstigeto give
8. 8
   workup.STIRRINGThe reaction is stirred at room temperature for 1 hour (LC-MS monitoring: complete conversion)
9. 9
   Sonstigesolvent is separated
10. 10
    SonstigeThe gummy solid is triturated with hexane
11. 11
    Sonstigeto give C25

Vorschrift

A mixture of 2-(tert-butoxycarbonylamino)-2-phenylacetic acid (0.90 g, 4.18 mmol), HOBt (0.68 g, 12.5 mmol), DCC (1.29 g, 6.27 mmol) and 3(R)-quinuclidinol (1.59 g, 12.5 mmol) in dry THF (50 mL) is stirred at room temperature for 16 hours (LC-MS monitoring: complete conversion). The solvent is removed under reduced pressure, the residue is taken up with EtOAc and washed twice with 2M K2CO3. The organic phase is dried over Na2SO4, filtered and evaporated to dryness. The compound is triturated with hexane to give (R)-quinuclidin-3-yl 2-(tert-butoxycarbonylamino)-2-phenylacetate as a white solid (1.46 g; 97% yield, mixture of diastereoisomers). This compound is dissolved in DCM (50 mL) and 4N HCl dioxane (5 mL) is added. The reaction is stirred at room temperature for 1 hour (LC-MS monitoring: complete conversion) and then solvent is separated. The gummy solid is triturated with hexane to give C25 as a white solid (1.26 g, 94% yield, di hydrochloride, mixture of diastereoisomers).

Quelle