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

HRID 1691603Notes

Reaction equation

HRID 1691603 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-fluorobenzyl)-1H-indole-2-carboxylate (WO2006/024776) 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 two times 100 ml of ethyl ether, acidified by successive additions of small amounts of concentrated hydrochloric acid and then extracted with 200 ml of ethyl acetate. The organic phase is finally washed with twice 100 ml of water, once with 50 ml of saturated sodium chloride solution, and dried over magnesium sulfate and concentrated under reduced pressure. This gives, after drying at 50° C. under reduced pressure, 6.4 g of the expected product, in the form of a solid which will be used as it is in the remainder of the synthesis.

Workup

  1. temperatureThe mixture is heated for two hours
  2. concentrationconcentrated under reduced pressure
  3. washThe solution is washed with two times 100 ml of ethyl ether
  4. extractionextracted with 200 ml of ethyl acetate
  5. washThe organic phase is finally washed with twice 100 ml of water, once with 50 ml of saturated sodium chloride solution
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. dry with materialThis gives, after drying at 50° C. under reduced pressure, 6.4 g of the expected product, in the form of a solid which
  9. customis in the remainder of the synthesis

Sources & evidence

ORD record
ord-ed7f0e8e85674d0497c2f70a53bb8b52
Source dataset
uspto-grants-2012_04
Patent number
US08153796B2

Reaction notes

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