Reacción #164201

Ecuación de reacción

(R)-Quinuclidin-3-ol

DCC

HOBT

(R)-quinuclidin-3-ol

N-Ethyl-N-isopropylpropan-2-amine 2-(4-(methoxycarbonyl)phenyl)-2-(phenylamino)acetate

DCC

HOBT

→

desired compound

Rendimiento 21.0%

4-{[(R)-(1-aza-bicyclo[2.2.2]oct-3-yl)oxycarbonyl]-phenylamino-methyl}-benzoic acid methyl ester

Rendimiento 21.0%

Disolventes

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.STIRRINGthe mixture is further stirred for 24 hours
2. 2
   OtroThen THF is evaporated
3. 3
   workup.DISSOLUTIONthe residue is dissolved in EtOAc
4. 4
   Lavadowashed with NaHCO3, water and brine
5. 5
   SecadoThe organic phase is dried (Na2SO4)
6. 6
   Filtraciónfiltered
7. 7
   Otroevaporated
8. 8
   OtroThe crude is purified by preparative HPLC
9. 9
   OtroThe recovered fractions are evaporated
10. 10
    workup.DISSOLUTIONdissolved in EtOAc
11. 11
    Lavadowashed with sat. NaHCO3
12. 12
    SecadoThe organic phase is dried (Na2SO4)
13. 13
    Filtraciónfiltered
14. 14
    Otroevaporated

Procedimiento

N-Ethyl-N-isopropylpropan-2-amine 2-(4-(methoxycarbonyl)phenyl)-2-(phenylamino)acetate (I94) (212 mg, 0.51 mmol), DCC (158 mg, 0.77 mmol), and HOBT (117 mg, 0.77 mmol) are dissolved in dry THF (5 mL). (R)-Quinuclidin-3-ol (195 mg, 1.53 mmol) is added and the mixture is stirred at RT for 2 days. A second portion of DCC (79 mg, 0.38 mmol), HOBT (58.7 mg, 0.38 mmol) and (R)-quinuclidin-3-ol (98 mg, 0.77 mmol) are added and the mixture is further stirred for 24 hours. Then THF is evaporated, the residue is dissolved in EtOAc and washed with NaHCO3, water and brine. The organic phase is dried (Na2SO4), filtered and evaporated. The crude is purified by preparative HPLC. The recovered fractions are evaporated, dissolved in EtOAc and washed with sat. NaHCO3. The organic phase is dried (Na2SO4), filtered and evaporated to afford the desired compound as a colorless oil (42 mg, 21% yield, mixture of diastereoisomers).

Fuente