Water → 3-(5-fluoro-1-methyl-1H-indol-3-yl)cyclopentanone

HRID 1072446Notes

Reaction equation

HRID 1072446 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH:8]=[C:7]2[CH:13]1[CH2:17][CH2:16][C:15](=[O:18])[CH2:14]1.I[CH3:20].O>CN(C)C=O>[F:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH3:20])[CH:8]=[C:7]2[CH:13]1[CH2:17][CH2:16][C:15](=[O:18])[CH2:14]1

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 221394665-Fluoro-3-(3-oxycyclopentyl)indole

Product 1

HCID 221491463-(5-fluoro-1-methyl-1H-indol-3-yl)cyclopentanoneYield 81%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A suspension of sodium hydride (60% dispersion in oil, 0.335 g, 8.2 mmol) in dimethylformamide (20 mL) was stirred at room temperature. A solution of 3-(5-fluoro-1H-indol-3-yl)-cyclopentanone (1.5 g, 6.9 mmol) in 10 mL of DMF was added dropwise over 10 min. The reaction mixture was stirred at room temperature for an additional 30 min, then iodomethane (3.1 g, 21.8 mmol) was added. After stirring at room temperature for 24 hours, the reaction mixture was poured into water (100 mL) and extracted with ethyl acetate (2×100 mL). The combined organic layers were washed with water (50 mL) and brine (50 mL), then were dried over anhydrous sodium sulfate, filtered, and concentrated to give 1.6 g of crude product. Flash chromatography on silica gel (50% ethyl acetate/hexane) afforded 1.2 g (81%) of the title compound as a thick oil which solidified on standing. An analytical sample was recrystallized from ethyl acetate/hexane: mp 104-105° C.; MS (ESI) m/z 232 [M+H]+.

Workup

  1. stirringThe reaction mixture was stirred at room temperature for an additional 30 min
  2. stirringAfter stirring at room temperature for 24 hours
  3. extractionextracted with ethyl acetate (2×100 mL)
  4. washThe combined organic layers were washed with water (50 mL) and brine (50 mL)
  5. dry with materialwere dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give 1.6 g of crude product

Sources & evidence

ORD record
ord-9cb1986537c346d7a48bfdb172e44118
Source dataset
uspto-grants-2005_06
Patent number
US06911445B2

Reaction notes

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