반응 #164201

반응 방정식

(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

수율 21.0%

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

수율 21.0%

용매

THF

반응 조건

후처리

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

실험 절차

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).

출처