تفاعل #164201

معادلة التفاعل

(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

المردود 21.0%

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

المردود 21.0%

المذيبات

THF

ظروف التفاعل

المعالجة

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

الإجراء التجريبي

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).

المصدر