Hydrochloric Acid → 5,6-Difluoroindoline

HRID 74566Notes

Reaction equation

HRID 74566 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[F:11])[NH:7][C:6](=O)[CH2:5]2.B.CO.Cl>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[F:11])[NH:7][CH2:6][CH2:5]2

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 6331BoraneHCID 125852825,6-Difluorooxindole

Product 1

HCID 167925945,6-Difluoroindoline

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Under an argon atmosphere 0.30 g (1.8 mmol) 5,6-difluoro-1,3-dihydro-indol-2-one were dissolved in 10 mL THF and 3.0 mL of a 1 M borane in THF solution were added dropwise. Then the reaction mixture was heated for 2 h to 70° C. and then cooled. After the addition of 3 mL MeOH a further 5 mL of a 4N aqueous hydrochloric acid solution were added and the mixture was refluxed for 1 h. The organic phase was evaporated down, the aqueous phase was washed with DCM and then made alkaline with a 4N aqueous sodium hydroxide solution and extracted several times with EtOAc. The combined organic phases were dried on sodium sulphate, filtered and evaporated down.

Workup

  1. temperatureThen the reaction mixture was heated for 2 h to 70° C.
  2. temperaturecooled
  3. additionwere added
  4. temperaturethe mixture was refluxed for 1 h
  5. customThe organic phase was evaporated down
  6. washthe aqueous phase was washed with DCM
  7. extractionextracted several times with EtOAc
  8. customThe combined organic phases were dried on sodium sulphate
  9. filtrationfiltered
  10. customevaporated down

Sources & evidence

ORD record
ord-5da8d5483d224c6ea5865e5cc88734ee
Source dataset
uspto-grants-2014_09
Patent number
US08829006B2

Reaction notes

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