Phenol → 1,3-Dihydro-1-[(3-fluoro-4-pyridinyl)propylamino]-2H-indol-2-one

HRID 53947Notes

Reaction equation

HRID 53947 reaction equation
[CH2:1]([NH:4][N:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7][C:6]1=[O:14])[CH2:2][CH3:3].C1(O)C=CC=CC=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.Cl.Cl[C:36]1[CH:41]=[CH:40][N:39]=[CH:38][C:37]=1[F:42].ClC1C=CN=CC=1F.C(=O)(O)[O-].[Na+]>ClCCl>[F:42][C:37]1[CH:38]=[N:39][CH:40]=[CH:41][C:36]=1[CH2:3][CH2:2][CH2:1][NH:4][N:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7][C:6]1=[O:14]

Participants

8

Reactant 6

HCID 996PhenolHCID 516892Sodium BicarbonateHCID 521998p-Toluenesulfonic acid monohydrateHCID 38524294-Chloro-3-fluoropyridineHCID 157036281-(Propylamino)-oxindoleHCID 193602344-Chloro-3-fluoropyridine hydrochloride

Product 1

HCID 677136721,3-Dihydro-1-[(3-fluoro-4-pyridinyl)propylamino]-2H-indol-2-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
150 °C

Procedure

To a stirred solution consisting of 1,3-dihydro-1-propylamino-2H-indol-2-one (5.06 g), phenol (13.2 g) and p-toluenesulfonic acid hydrate (0.25 g), heated at 150° C., was added 4-chloro-3-fluoropyridine hydrochloride (5.37 g). Heating was continued at 150° C. for 10.75 hours at which time additional 4-chloro-3-fluoropyridine (2.05 g) was added and heating continued an additional 6.5 hours. Upon cooling to room temperature, the reaction mixture was dissolved in dichloromethane and dilute aqueous sodium bicarbonate. The layers were separated and the organic layer extracted with dilute aqueous sodium bicarbonate (2×). The combined aqueous layers were back-extracted with dichloromethane and ether. The combined organic layers were washed with brine, dried (K2CO3), filtered, and concentrated. Purification via flash column chromatography (silica gel, 2% triethylamine/ether) and another column (silica gel, EtOAc) afforded the desired product as a solid.

Workup

  1. temperatureHeating
  2. additionwas added
  3. temperatureheating
  4. temperatureUpon cooling to room temperature
  5. customThe layers were separated
  6. extractionthe organic layer extracted with dilute aqueous sodium bicarbonate (2×)
  7. extractionThe combined aqueous layers were back-extracted with dichloromethane and ether
  8. washThe combined organic layers were washed with brine
  9. dry with materialdried (K2CO3)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customPurification via flash column chromatography (silica gel, 2% triethylamine/ether)

Sources & evidence

ORD record
ord-4377afc7093f4343ac4061e0caecdfaa
Source dataset
uspto-grants-1997_04
Patent number
US05621116

Reaction notes

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