تفاعل #164191

معادلة التفاعل

(4-fluoro-benzylamino)-phenyl-acetic acid hydrochloride

(R)-quinuclidin-3-ol

HOBT

→

title compound

المردود 21.0%

(4-fluoro-benzylamino)-phenyl-acetic acid (R)-(1-aza-bicyclo[2.2.2]oct-3-yl)ester

المردود 21.0%

المذيبات

acetonitrile

ظروف التفاعل

المعالجة

1. 1
   أخرىTHF is removed under vacuum
2. 2
   أخرىthe crude is partitioned between EtOAc and water
3. 3
   تجفيفThe organic phase is dried over sodium sulphate
4. 4
   ترشيحfiltered
5. 5
   أخرىevaporated to dryness
6. 6
   أخرىThe crude is purified by preparative HPLC
7. 7
   أخرىThe combined fractions are dried
8. 8
   أخرىpartitioned between EtOAc and 2M K2CO3
9. 9
   تجفيفThe organic phase is dried over sodium sulphate
10. 10
    ترشيحfiltered
11. 11
    أخرىevaporated to dryness

الإجراء التجريبي

A mixture of (4-fluoro-benzylamino)-phenyl-acetic acid hydrochloride (233 mg, 0.79 mmol), (R)-quinuclidin-3-ol (200 mg, 1.57 mmol), 2-(1H-benzo[d][1,2,3]triazol-1-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate(V) (596 mg, 1.57 mmol), TEA (0.22 mL, 1.57 mmol) and HOBT (241 mg, 1.57 mmol) in acetonitrile (10 mL) is stirred at RT for 48 hours. THF is removed under vacuum and the crude is partitioned between EtOAc and water. The organic phase is dried over sodium sulphate, filtered and evaporated to dryness. The crude is purified by preparative HPLC. The combined fractions are dried and partitioned between EtOAc and 2M K2CO3. The organic phase is dried over sodium sulphate, filtered and evaporated to dryness to achieve the title compound as colorless oil (61 mg, 21% yield, mixture of diastereoisomers).

المصدر