Hydrochloric Acid → (2-Fluorophenyl)(1-methylpiperidin-4-yl)methanone--hydrogen chloride (1/1)

HRID 1248400Notes

Reaction equation

HRID 1248400 reaction equation
[Mg].[CH3:2][N:3]1[CH2:8][CH2:7][CH:6]([Cl:9])[CH2:5][CH2:4]1.[F:10][C:11]1[CH:18]=[CH:17][CH:16]=[CH:15][C:12]=1[C:13]#N.[Cl-].[NH4+].Cl.[O:22]1CCCC1>C(Br)C.CCOCC>[ClH:9].[F:10][C:11]1[CH:18]=[CH:17][CH:16]=[CH:15][C:12]=1[C:13]([CH:6]1[CH2:7][CH2:8][N:3]([CH3:2])[CH2:4][CH2:5]1)=[O:22]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 8028Tetrahydrofuran3×HCID 25517Ammonium ChlorideHCID 678552-FluorobenzonitrileHCID 793424-chloro-N-methylpiperidineHCID 5462224Magnesium

Product 1

HCID 13180318(2-Fluorophenyl)(1-methylpiperidin-4-yl)methanone--hydrogen chloride (1/1)Yield 42%

Reagents, catalysts & solvents 2

HCID 6332Ethyl BromideCatalystHCID 3283Diethyl EtherSolvent

Procedure

To a suspension of 7.6 of magnesium turnings in 25 ml of tetrahydrofuran was added a few drops of ethyl bromide, with stirring under nitrogen. After the reaction began approximately 50.0 g of N-methyl-4-chloropiperidine in 125 ml of tetrahydrofuran was added dropwise at a rate such that moderate reflux was maintained. The reaction mixture was heated under reflux for an additional hour. A solution of 37.2 g of 2-fluorobenzonitrile in 30 ml of tetrahydrofuran was added dropwise. After completion of the addition, the reaction mixture was heated under reflux for two hrs and stirred overnight at room temperature. The reaction mixture was poured into a solution of 85 g of ammonium chloride in 1200 ml of ice water and heated on a steam bath for 3 hrs. The mixture was cooled, extracted with benzene (3×250 ml) and dried over anhydrous sodium sulfate. Removal of the solvent under reduced pressure gave an oil. A 1.0 g-portion of the oil was dissolved in ether and a solution of ethereal hydrogen chloride was added. The precipitate was collected, dried and twice recrystallized from ethanol-ether to give 0.5 g (42%) of product as crystals, mp 167°-169°.

Workup

  1. additionwas added dropwise at a rate such
  2. temperaturethat moderate reflux
  3. temperaturewas maintained
  4. temperatureThe reaction mixture was heated
  5. temperatureunder reflux for an additional hour
  6. additionAfter completion of the addition
  7. temperaturethe reaction mixture was heated
  8. temperatureunder reflux for two hrs
  9. stirringstirred overnight at room temperature
  10. temperatureheated on a steam bath for 3 hrs
  11. temperatureThe mixture was cooled
  12. extractionextracted with benzene (3×250 ml)
  13. dry with materialdried over anhydrous sodium sulfate
  14. customRemoval of the solvent under reduced pressure
  15. customgave an oil
  16. customThe precipitate was collected
  17. customdried
  18. customtwice recrystallized from ethanol-ether

Sources & evidence

ORD record
ord-ae239382dad546a4bae03a7b85f266bb
Source dataset
uspto-grants-1985_06
Patent number
US04524074

Reaction notes

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