1-Hydroxybenzotriazole → 2-({[(R)-(1-aza-bicyclo[2.2.2]oct-3-yl)oxycarbonyl]-phenyl-methyl}-amino)-benzoic acid methyl ester

N-ethyl-N-isopropylpropan-2-amine 2-(2-(methoxycarbonyl)phenylamino)-2-phenylacetate (I34) (611 mg, 1.47 mmol), 2-(1H-benzo[d][1,2,3]triazol-1-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate(V) (559 mg, 1.47 mmol), and HOBT (226 mg, 1.47 mmol) are dissolved in THF (7 mL) and MeCN (3 mL). (R)-Quinuclidin-3-ol (375 mg, 2.95 mmol) is added and the mixture is stirred at RT for 1 hour. Solvents are evaporated, the residue is dissolved in EtOAc and washed with sat. NaHCO3, water and brine. The organic layer is recovered, dried over Na2SO4, filtered and evaporated. The crude is purified by preparative HPLC and the collected fractions are evaporated, the residue is dissolved in EtOAc and washed with NaHCO3 and brine. The organic layer is recovered, dried over Na2SO4, filtered and evaporated to afford compound the title compound as a colorless compound (95 mg, 16% yield, mixture of diastereoisomers).

1. customSolvents are evaporated
2. dissolutionthe residue is dissolved in EtOAc
3. washwashed with sat. NaHCO3, water and brine
4. customThe organic layer is recovered
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. customevaporated
8. customThe crude is purified by preparative HPLC
9. customthe collected fractions are evaporated
10. dissolutionthe residue is dissolved in EtOAc
11. washwashed with NaHCO3 and brine
12. customThe organic layer is recovered
13. dry with materialdried over Na2SO4
14. filtrationfiltered
15. customevaporated

ORD 기록

ord-1356093da1324836bc8a0daf4a9f0b7c

출처 데이터셋

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08835682B2