反应 #164201

反应方程式

(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

收率 21.0%

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

收率 21.0%

溶剂

THF

反应条件

后处理

1. 1
   workup.STIRRINGthe mixture is further stirred for 24 hours
2. 2
   其他Then THF is evaporated
3. 3
   workup.DISSOLUTIONthe residue is dissolved in EtOAc
4. 4
   洗涤washed with NaHCO3, water and brine
5. 5
   干燥The organic phase is dried (Na2SO4)
6. 6
   过滤filtered
7. 7
   其他evaporated
8. 8
   其他The crude is purified by preparative HPLC
9. 9
   其他The recovered fractions are evaporated
10. 10
    workup.DISSOLUTIONdissolved in EtOAc
11. 11
    洗涤washed with sat. NaHCO3
12. 12
    干燥The organic phase is dried (Na2SO4)
13. 13
    过滤filtered
14. 14
    其他evaporated

实验过程

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).

来源