Phenol → 1,3-dihydro-1-(propyl-4-pyridinylamino)-2H-indol-2-one

HRID 1646260Notes

Reaction equation

HRID 1646260 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.Cl.Br[C:24]1[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=1.[OH-].[Na+]>>[CH2:1]([N:4]([C:24]1[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=1)[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]

Participants

5

Reactant 4

HCID 996PhenolHCID 14798Sodium HydroxideHCID 881004-Bromopyridinium chlorideHCID 157036281-(Propylamino)-oxindole

Product 1

HCID 149942611,3-dihydro-1-(propyl-4-pyridinylamino)-2H-indol-2-oneYield 14.4%

Procedure

To a stirred solution of 1,3-dihydro-1-(propylamino)-2H-indol-2-one (10.4 g) and phenol (30.8 g), preheated to 150° C. under nitrogen, was added 4-bromopyridine hydrochloride (11.04 g) over 5 min. Heating was continued for 7 hours at which time the reaction mixture was cooled to room temperature and made basic by slow addition of dilute aqueous sodium hydroxide. The product was extracted four times with ethyl acetate and the combined organic layers back-extracted with dilute aqueous sodium hydroxide, washed with brine, and dried (K2CO3). Filtration and concentration gave the crude product. Purification via flash column chromatography (silica gel, EtOAc), preparative high performance liquid chromatography (HPLC) (silica gel, EtOAc→2% Et3N/0-7% MeOH/EtOAc), and a third column (alumina, EtOAc) followed. Recrystallization from ethyl acetate-pentane afforded 2.10 g (14%) of 1,3-dihydro-1-(propyl-4-pyridinylamino)-2H-indol-2-one, as a solid, m.p. 140°-143° C.

Workup

  1. custompreheated to 150° C. under nitrogen
  2. temperatureHeating
  3. extractionThe product was extracted four times with ethyl acetate
  4. extractionthe combined organic layers back-extracted with dilute aqueous sodium hydroxide
  5. washwashed with brine
  6. dry with materialdried (K2CO3)
  7. filtrationFiltration and concentration
  8. customgave the crude product
  9. customPurification via flash column chromatography (silica gel, EtOAc), preparative high performance liquid chromatography (HPLC) (silica gel, EtOAc→2% Et3N/0-7% MeOH/EtOAc)
  10. customRecrystallization from ethyl acetate-pentane

Sources & evidence

ORD record
ord-c05b149d58d44510973872a60550ba1e
Source dataset
uspto-grants-1993_01
Patent number
US05179119

Reaction notes

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