Triethylsilane → [3-(2-Benzenesulfonyl-pyridin-3-ylmethyl)-5-fluoro-2-methyl-indol-1-yl]-acetic acid ethyl ester

온도

0 °C

A solution of (5-fluoro-2-methyl-indol-1-yl)-acetic acid ethyl ester (0.95 g, 4.04 mmol), prepared as described in Example 1 of WO/2006/092579, and 2-(benzenesulfonyl)isonicotinaldehyde (1.0 g, 4.04 mmol) in dry dichloromethane (45 ml) was added slowly over 5 minutes to a stirred solution of TMSOTf (1.46 ml, 8.08 mmol) in dry dichloromethane (12.5 ml) cooled to 0° C. under N2. This mixture was stirred for 15 minutes and triethylsilane (1.94 ml, 12.12 mmol) was added in one portion. The reaction mixture was stirred for 2 h 30 minutes, warmed to room temperature, and quenched by the slow addition of saturated aqueous NaHCO3 (10 ml). The resulting biphasic mixture was extracted with dichloromethane. The combined organic layers were washed with brine, dried over anhydrous MgSO4, filtered and evaporated. The resulting solid was purified by column chromatography eluting with ethyl acetate:hexanes 0:100 to 60:40 v/v to afford 1.21 g (64%) of the title compound (LCMS RT=6.63 min, MH+466.8).

1. stirringThe reaction mixture was stirred for 2 h 30 minutes
2. temperaturewarmed to room temperature
3. customquenched by the slow addition of saturated aqueous NaHCO3 (10 ml)
4. extractionThe resulting biphasic mixture was extracted with dichloromethane
5. washThe combined organic layers were washed with brine
6. dry with materialdried over anhydrous MgSO4
7. filtrationfiltered
8. customevaporated
9. customThe resulting solid was purified by column chromatography
10. washeluting with ethyl acetate:hexanes 0:100 to 60:40 v/v

ORD 기록

ord-2d0d37dd0e064e73940bb5d1cbcc1cad

출처 데이터셋

uspto-grants-2010_07

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07750027B2