反応 #164201

反応方程式

(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

収率 21.0%

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

収率 21.0%

溶媒

THF

反応条件

後処理

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

実験手順

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).

出典