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

HRID 874697Notes

Reaction equation

HRID 874697 reaction equation
[CH2:1]([O:3][C:4](=[O:17])[CH2:5][N:6]1[C:14]2[C:9](=[CH:10][C:11]([F:15])=[CH:12][CH:13]=2)[CH:8]=[C:7]1[CH3:16])[CH3:2].[C:18]1([S:24]([C:27]2[CH:28]=[C:29]([CH:32]=[CH:33][N:34]=2)C=O)(=[O:26])=[O:25])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[Si](OS(C(F)(F)F)(=O)=O)(C)(C)[CH3:36].C([SiH](CC)CC)C>ClCCl>[CH2:1]([O:3][C:4](=[O:17])[CH2:5][N:6]1[C:14]2[C:9](=[CH:10][C:11]([F:15])=[CH:12][CH:13]=2)[C:8]([CH2:36][C:28]2[C:27]([S:24]([C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)(=[O:25])=[O:26])=[N:34][CH:33]=[CH:32][CH:29]=2)=[C:7]1[CH3:16])[CH3:2]

Participants

6

Reactant 4

HCID 12052TriethylsilaneHCID 65367Trimethylsilyl triflateHCID 44185546Ethyl 2-(5-fluoro-2-methyl-1H-indol-1-yl)acetateHCID 866328282-(Benzenesulfonyl)isonicotinaldehyde

Product 1

HCID 59380589[3-(2-Benzenesulfonyl-pyridin-3-ylmethyl)-5-fluoro-2-methyl-indol-1-yl]-acetic acid ethyl esterYield 64.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-d0cfbf74145541d88b6e092a363f2769
Source dataset
uspto-grants-2015_03
Patent number
US08980927B2

Reaction notes

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