تفاعل #164197

معادلة التفاعل

(R)-quinuclidin-3-ol

HOBT

DCC

(R)-quinuclidin-3-ol

2-(Phenylamino)-2-(thiophen-2-yl)acetic acid hydrochloride

DCC

HOBT

HOBT

DCC

→

title compound

المردود 7.0%

(R)-quinuclidin-3-yl 2-(phenylamino)-2-(thiophen-2-yl)acetate hydrochloride

المردود 7.0%

المذيبات

THF

ظروف التفاعل

المعالجة

1. 1
   workup.STIRRINGthe mixture is stirred for additional 8 hours
2. 2
   workup.STIRRINGthe mixture is stirred for additional 16 hours
3. 3
   أخرىTHF is evaporated
4. 4
   workup.DISSOLUTIONthe resulting crude oil is dissolved in EtOAc
5. 5
   غسيلwashed with water and brine
6. 6
   أخرىThe organic phase is recovered
7. 7
   تجفيفdried over Na2SO4
8. 8
   ترشيحfiltered
9. 9
   أخرىevaporated
10. 10
    أخرىThe crude is first purified by flash chromatography (DCM/MeOH=9/1)
11. 11
    أخرىThe pure fractions are collected
12. 12
    أخرىevaporated
13. 13
    workup.DISSOLUTIONThe resulting TFA salt is dissolved in THF
14. 14
    أخرىTHF is evaporated
15. 15
    workup.DISSOLUTIONthe product is dissolved in dioxane (2 mL)
16. 16
    workup.ADDITION4M HCl in dioxane (2 mL) is added
17. 17
    أخرىThe solvent is evaporated
18. 18
    أخرىthe residue is dried under vacuum for 24 h

الإجراء التجريبي

2-(Phenylamino)-2-(thiophen-2-yl)acetic acid hydrochloride (I89) (359 mg, 1.33 mmol), DCC (330 mg, 1.60 mmol) and HOBT (245 mg, 1.60 mmol) are dissolved in THF (15 mL). (R)-quinuclidin-3-ol (339 mg, 2.66 mmol) is added and the reaction mixture is stirred at RT for 16 hours. HOBT (20.4 mg, 0.13 mmol) and DCC (33.0 mg, 0.16 mmol) are added again and the mixture is stirred for additional 8 hours. HOBT (20.4 mg, 0.13 mmol), DCC (33.0 mg, 0.16 mmol), (R)-quinuclidin-3-ol (16.9 mg, 0.13 mmol) are added and the mixture is stirred for additional 16 hours. THF is evaporated and the resulting crude oil is dissolved in EtOAc and washed with water and brine. The organic phase is recovered, dried over Na2SO4, filtered and evaporated. The crude is first purified by flash chromatography (DCM/MeOH=9/1) and then by preparative HPLC. The pure fractions are collected and evaporated. The resulting TFA salt is dissolved in THF and passed through a PL-HCO3 cartridge (Varian, 200 mg, 1.8 mmol/g HCO3−). THF is evaporated, the product is dissolved in dioxane (2 mL) and 4M HCl in dioxane (2 mL) is added. The solvent is evaporated and the residue is dried under vacuum for 24 h to obtain the title compound as a brown solid (33 mg, 7% yield, mixture of disateroisomers).

المصدر