Potassium Iodide → 1-(2-(4-(4-Fluorobenzoyl)piperidin-1-yl)ethyl)-3,3-dimethylindolin-2-one hydrochloride

HRID 965283Notes

Reaction equation

HRID 965283 reaction equation
[CH3:1][C:2]1([CH3:15])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]([CH2:11][CH2:12]O)[C:3]1=[O:14].C([N:18]([CH2:21][CH3:22])[CH2:19][CH3:20])C.CS([Cl:27])(=O)=O.[C:28]1(C)C=CC(S(O)(=O)=O)=CC=1.[F:39][C:40]1[CH:53]=[CH:52][C:43]([C:44](N2CCCCC2)=[O:45])=[CH:42][CH:41]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>ClCCl.C(Cl)(Cl)Cl>[ClH:27].[CH3:1][C:2]1([CH3:15])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]([CH2:11][CH2:12][N:18]2[CH2:19][CH2:20][CH:28]([C:44](=[O:45])[C:43]3[CH:42]=[CH:41][C:40]([F:39])=[CH:53][CH:52]=3)[CH2:22][CH2:21]2)[C:3]1=[O:14]

Participants

9

Reactant 6

HCID 4875Potassium IodideHCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 158173642-((3,3-Dimethyl)oxindolyl)ethanolHCID 187806554-Fluorobenzoylpiperidine para toluenesulfonate

Product 1

HCID 119575761-(2-(4-(4-Fluorobenzoyl)piperidin-1-yl)ethyl)-3,3-dimethylindolin-2-one hydrochloride

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Procedure

3,3-Dimethyl-1-(2-hydroxyethyl)-1,3-dihydro-2H-indol-2-one (2.05 g, 10 mmol) and triethylamine (1.1 g, 10.9 mmol) was dissolved in dichloromethane under nitrogen and cooled to less than 5° C. in an ice/water bath. Methanesulfonyl chloride (1.3 g, 11.3 mmol) was added and the mixture was stirred for one hour with cooling. The mixture was washed with cold dilute hydrochloric acid, dried (MgSO4), filtered and concentrated under reduced pressure. The resulting oil was dissolved in dry acetonitrile, 4-fluorobenzoylpiperidine para toluenesulfonate (Acros, 2.83 g, 11.7 mmol) potassium carbonate (3 g, 21.7 mmol) and potassium iodide (0.15 g, 0.9 mmol) were added. The mixture was stirred vigorously and heated under gentle reflux for two days. The mixture was poured into chloroform, washed with water, dried (MgSO4), filtered and concentrated under reduced pressure. The resulting oil was taken up in 5N hydrochloric acid whereupon a white solid separated. This solid was recrystallised from ethanol to give 3,3-dimethyl-1-{2-[4-(4-fluorobenzoyl)-1-piperidinyl]-1-ethyl}-1,3-dihydro-2H-indol-2-one monohydrochloride. Melting point 236°-8° C.

Workup

  1. temperaturecooled to less than 5° C. in an ice/water bath
  2. temperaturewith cooling
  3. washThe mixture was washed with cold dilute hydrochloric acid
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe resulting oil was dissolved in dry acetonitrile
  8. stirringThe mixture was stirred vigorously
  9. temperatureheated
  10. temperatureunder gentle reflux for two days
  11. washwashed with water
  12. dry with materialdried (MgSO4)
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure
  15. customseparated
  16. customThis solid was recrystallised from ethanol

Sources & evidence

ORD record
ord-516d63b6b3784888a3d856b82b683feb
Source dataset
uspto-grants-1998_06
Patent number
US05773448

Reaction notes

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