Sodium Hydroxide → 5-fluoro-1-(3-fluorobenzyl)-1H-indole-2-carboxylic acid

HRID 1943984Notes

Reaction equation

HRID 1943984 reaction equation
[OH-].[Na+].[F:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=1)[C:8]([C:21]([O:23]CC)=[O:22])=[CH:7]2>O.C(O)C>[F:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=1)[C:8]([C:21]([OH:23])=[O:22])=[CH:7]2

Participants

5

Reactant 2

HCID 14798Sodium Hydroxide2×HCID 57431514Ethyl 5-fluoro-1-(3-fluorobenzyl)-1H-indole-2-carboxylate

Product 1

HCID 574315135-fluoro-1-(3-fluorobenzyl)-1H-indole-2-carboxylic acid

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

An aqueous sodium hydroxide solution, prepared from 1.15 g (28.92 mmol) of sodium hydroxide pellets in 50 mL of water, is added to a solution of 7.6 g (24.10 mmol) of ethyl 5-fluoro-1-[(3-fluorophenyl)methyl]-1H-indole-2-carboxylate (WO 2006/024776) in 241 mL of ethanol. The mixture is heated for two hours and then concentrated under reduced pressure. The resulting solid is taken up in 200 mL of water. The solution is washed with twice 100 mL of ethyl ether, acidified by successive addition of small amounts of concentrated hydrochloric acid and then extracted with 200 mL of ethyl acetate. The organic phase is finally washed twice with 100 mL of water, once with 50 ml of saturated sodium chloride solution, dried over magnesium sulfate and concentrated under reduced pressure. After drying at 50° C. under reduced pressure, 6.4 g of the expected product are obtained in the form of a solid, which is used without further purification in the rest of the synthesis.

Workup

  1. temperatureThe mixture is heated for two hours
  2. concentrationconcentrated under reduced pressure
  3. washThe solution is washed with twice 100 mL of ethyl ether
  4. additionacidified by successive addition of small amounts of concentrated hydrochloric acid
  5. extractionextracted with 200 mL of ethyl acetate
  6. washThe organic phase is finally washed twice with 100 mL of water, once with 50 ml of saturated sodium chloride solution
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. dry with materialAfter drying at 50° C. under reduced pressure, 6.4 g of the expected product
  10. customare obtained in the form of a solid, which
  11. customis used without further purification in the rest of the synthesis

Sources & evidence

ORD record
ord-b677a530a8cb4c24a998e63e6bb31ea6
Source dataset
uspto-grants-2013_03
Patent number
US08394820B2

Reaction notes

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