Iodine → (2-Aminophenyl)(1-methylpiperidin-4-yl)methanone

HRID 406830Notes

Reaction equation

HRID 406830 reaction equation
[Mg].Cl[CH:3]1[CH2:8][CH2:7][N:6]([CH3:9])[CH2:5][CH2:4]1.II.C1([Mg]Cl)CCCCC1.[NH2:20][C:21]1[CH:28]=[CH:27][CH:26]=[CH:25][C:22]=1[C:23]#N.C1C[O:32]CC1>>[NH2:20][C:21]1[CH:28]=[CH:27][CH:26]=[CH:25][C:22]=1[C:23]([CH:3]1[CH2:8][CH2:7][N:6]([CH3:9])[CH2:5][CH2:4]1)=[O:32]

Participants

7

Reactant 6

HCID 807IodineHCID 8028Tetrahydrofuran2×HCID 729132-AminobenzonitrileHCID 793424-chloro-N-methylpiperidineHCID 5462224MagnesiumHCID 178478990HCID 178478990, compound

Product 1

HCID 21414385(2-Aminophenyl)(1-methylpiperidin-4-yl)methanoneYield 7%

Conditions

Temperature
45 °C

Procedure

To a suspension of magnesium (1.8 g, 74 mmol) in dry THF (50 mL) in a flame-dried round bottomed flask under nitrogen was added 4-chloro-1-methylpiperidine (9.0 g, 68 mmol). A crystal of iodine and a catalytic amount of cyclohexylmagnesium chloride was added and the mixture was heated to reflux for 2 h. A gray precipitate formed, which was removed via vacuum filtration under a nitrogen atmosphere. To the filtrate was added a solution of 2-aminobenzonitrile (1.6 g, 14 mmol) in dry THF (15 mL). The stirred mixture was heated to 45° C. for 2 h. Ice was added and the reaction was quenched with 1 M sulfuric acid. The mixture was extracted with ethyl acetate and the acidic aqueous layer was then neutralized with 1 N sodium hydroxide, concentrated on a rotary evaporator and extracted with ethyl acetate. The combined organics were dried over sodium sulfate, filtered and concentrated to afford (2-aminophenyl)(1-methylpiperidin-4-yl)methanone as a yellow oil (1.0 g, 7%).

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 2 h
  3. customA gray precipitate formed
  4. customwhich was removed via vacuum filtration under a nitrogen atmosphere
  5. additionIce was added
  6. customthe reaction was quenched with 1 M sulfuric acid
  7. extractionThe mixture was extracted with ethyl acetate
  8. concentrationconcentrated on a rotary evaporator
  9. extractionextracted with ethyl acetate
  10. dry with materialThe combined organics were dried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-3fa4b64c39b34396a2fc3cf93cad6edc
Source dataset
uspto-grants-2014_06
Patent number
US08754092B2

Reaction notes

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