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

Temperature

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 record

ord-14db29513ab5489cb8c3ef5dc8801799

Source dataset

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08536158B2