Potassium Hydroxide → 5-Fluoro-1-(3-fluorobenzyl)-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acid

HRID 1019588Notes

Reaction equation

HRID 1019588 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[CH:10]=[CH:9][N:8]([CH2:11][C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=3)[C:5]2=[N:6][CH:7]=1.CC[C:21]([O-:23])=[O:22].[OH-].[K+]>C(O)C.O>[F:1][C:2]1[CH:3]=[C:4]2[CH:10]=[C:9]([C:21]([OH:23])=[O:22])[N:8]([CH2:11][C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=3)[C:5]2=[N:6][CH:7]=1

Participants

5

Reactant 2

HCID 14797Potassium HydroxideHCID 866390625-fluoro-1-(3-fluorobenzyl)-1H-pyrrolo[2,3-b]pyridine 2-ethyl carboxylate

Product 1

HCID 669079435-Fluoro-1-(3-fluorobenzyl)-1H-pyrrolo[2,3-b]pyridine-2-carboxylic acidYield 90.2%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

A mixture of 6.9 g (20.58 mmol) of 5-fluoro-1-(3-fluorobenzyl)-1H-pyrrolo[2,3-b]pyridine-2-ethyl carboxylate (WO07/010,138) and 1.89 g (33.7 mmol) of potassium hydroxide in a mixture of 80 mL of ethanol and 10 mL of water is heated under reflux for 1.5 h. After this time, the reaction mixture is concentrated at reduced pressure, and is then taken up in 200 mL of water. The solution is acidified with additions of concentrated hydrochloric acid, and then extracted three times with 50 mL of dichloromethane. The organic phases are combined, dried over sodium sulfate and then concentrated at reduced pressure. The resultant product is triturated in 5 mL of dichloromethane. A precipitate is collected by filtration and is dried at reduced pressure. In this way we isolate 5.35 g of the expected product, which is used as it is in the rest of the synthesis.

Workup

  1. temperatureis heated
  2. temperatureunder reflux for 1.5 h
  3. concentrationAfter this time, the reaction mixture is concentrated at reduced pressure
  4. extractionextracted three times with 50 mL of dichloromethane
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated at reduced pressure
  7. customThe resultant product is triturated in 5 mL of dichloromethane
  8. filtrationA precipitate is collected by filtration
  9. customis dried at reduced pressure

Sources & evidence

ORD record
ord-32e3f5a990c44f2ca519cdc595ddddd1
Source dataset
uspto-grants-2014_05
Patent number
US08716273B2

Reaction notes

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