Sodium ethoxide → 6-Fluoro-5-methoxy-1H-indole

HRID 1766218Notes

Reaction equation

HRID 1766218 reaction equation
[O-]CC.[Na+].C(OC(=O)[NH:9][C:10]1[CH:15]=[C:14]([F:16])[C:13]([O:17][CH3:18])=[CH:12][C:11]=1[C:19]#[C:20][Si](C)(C)C)C>C(O)C>[CH3:18][O:17][C:13]1[CH:12]=[C:11]2[C:10](=[CH:15][C:14]=1[F:16])[NH:9][CH:20]=[CH:19]2

Participants

4

Reactant 2

HCID 2723922Sodium ethoxideHCID 67441696HCID 67441696, compound

Product 1

HCID 178892306-Fluoro-5-methoxy-1H-indole

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent3×

Procedure

A solution of sodium ethoxide (formed by dissolving NaH 11.45 g, 60% in oil, 286.2 mmol, 4 eq.) in ethanol was poured into an EtOH solution of (5-fluoro-4-methoxy-2-trimethylsilanylethynyl-phenyl)-carbamic acid ethyl ester (22.14 g, 71.55 mmol) in EtOH (250 mL). The reaction was allowed to stir at room temperature for 2 hours and heated to 75° C. overnight. The EtOH was removed in vacuo and the residue diluted with water. The aqueous suspension was extracted 2×300 mL with Et2O. The organics were combined and washed with brine. The organic layer was collected, dried over MgSO4, filtered, and the solvent removed in vacuo leaving a dark red oil. The oil was purified by silica gel flash column chromatography using 15% EtOAc in hexanes as the mobile phase. Removal of the solvent in vacuo from the fractions containing the product left a golden yellow oil which solidified on standing: 1H NMR (300 MHz, CDCl3): 3.93 (s, 3H), 6.48 (m, 1H), 7.15 (m, 3H), 8.11 (bs, 1H); MS(ES+): m/z 166 (M+H)+; MS(ES−): m/z 164 (M−H)−; Calculated for C9H8FNO: C, 65.45; H, 4.88; N, 8.48; found: C, 65.17; H, 4.97; N, 8.70.

Workup

  1. temperatureheated to 75° C. overnight
  2. customThe EtOH was removed in vacuo
  3. additionthe residue diluted with water
  4. extractionThe aqueous suspension was extracted 2×300 mL with Et2O
  5. washwashed with brine
  6. customThe organic layer was collected
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. customthe solvent removed in vacuo
  10. customleaving a dark red oil
  11. customThe oil was purified by silica gel flash column chromatography
  12. customRemoval of the solvent in vacuo from the fractions
  13. additioncontaining the product
  14. waitleft a golden yellow oil which

Sources & evidence

ORD record
ord-7e2a80a3c9184a5cb9e4183a9695d595
Source dataset
uspto-grants-2007_06
Patent number
US07230011B2

Reaction notes

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