Hydrochloric Acid → di-tert-butyl (2S,2'S)-2,2'-{[(1S,4S)-1,4-dihydroxybutane-1,4-diyl]bis (6-fluoro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazole-5,2-diyl)}dipyrrolidine-1-carboxylate

온도

0 °C

To a solution of (R)-(+)-α,α-diphenyl-2-pyrrolidinemethanol (59.9 mg, 0.24 mmol) in THF (2.8 mL) was added trimethylborate (0.034 mL, 0.31 mmol), and the resultant solution was stirred for 90 minutes. The solution was cooled to 0° C. and N,N-diethylaniline borane (0.4 mL, 2.2 mmol) was added in portions over 30 minutes with stirring continued at 0° C. This solution was added via cannula to a 0° C. solution of di-tert-butyl (2S,2′S)-2,2′-[(1,4-dioxobutane-1,4-diyl)bis(6-fluoro-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazole-5,2-diyl)]dipyrrolidine-1-carboxylate (265 mg, 0.28 mmol) in THF (2.8 mL) and then warmed to room temperature and stirred for 16 hours. The solution was cooled to 0° C. and CH3OH (0.09 mL, 2.2 mmol) was added, and the solution was warmed to room temperature and stirred for 2 hours. 1N HCl was added, and the aqueous solution was extracted with EtOAc. The combined extracts were washed with brine, dried (Na2SO4), filtered and concentrated. Purification was run by flash chromatography (0-3% CH3OH/CH2Cl2) to give the title compound (248 mg, 0.26 mmol, 93%).

1. customcontinued at 0° C
2. temperaturewarmed to room temperature
3. stirringstirred for 16 hours
4. temperatureThe solution was cooled to 0° C.
5. temperaturethe solution was warmed to room temperature
6. stirringstirred for 2 hours
7. extractionthe aqueous solution was extracted with EtOAc
8. washThe combined extracts were washed with brine
9. dry with materialdried (Na2SO4)
10. filtrationfiltered
11. concentrationconcentrated
12. customPurification

ORD 기록

ord-ba38d52c4dff41d99d29d47f7a0af197

출처 데이터셋

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08937150B2