Iodine → HCID 22247874, compound

HRID 890024Notes

Reaction equation

HRID 890024 reaction equation
[Mg].II.[F:4][C:5]1[CH:12]=[CH:11][CH:10]=[CH:9][C:6]=1[CH2:7]Cl.CON(C)[C:16]([CH:18]1[CH2:23][CH2:22][CH2:21][N:20]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:19]1)=[O:17].[Cl-].[NH4+]>C(OCC)C.C(OCC)(=O)C>[C:27]([O:26][C:24]([N:20]1[CH2:21][CH2:22][CH2:23][CH:18]([C:16](=[O:17])[CH2:7][C:6]2[CH:9]=[CH:10][CH:11]=[CH:12][C:5]=2[F:4])[CH2:19]1)=[O:25])([CH3:30])([CH3:29])[CH3:28]

Participants

8

Reactant 5

HCID 807IodineHCID 9580Benzene, 1-(chloromethyl)-2-fluoro-2×HCID 25517Ammonium ChlorideHCID 5462224MagnesiumHCID 22248320Tert-butyl 3-[methoxy(methyl)carbamoyl]piperidine-1-carboxylate

Product 1

HCID 22247874HCID 22247874, compoundYield 27%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

After suspending 334 mg of magnesium in 3 ml of diethyl ether, a catalytic amount of iodine was added, a portion of 1.89 g of 2-fluorobenzyl chloride fleas added dropwise while stirring, and the mixture was heated to initiate the reaction. After adding 10 ml of diethyl ether, the remaining 2-fluorobenzyl chloride was added dropwise to maintain reflux. After stirring the mixture for 15 minutes, approximately 6 ml of the obtained reaction solution was added dropwise to a solution of 1.78 g of N-methoxy-N-methyl-1-(tert-butoxycarbonyl)-3-piperidinecarboxamide [CAS No.189442-78-2] in diethyl ether (20 ml) while cooling on ice, and stirring was continued for 30 minutes. Saturated aqueous ammonium chloride solution was added to the reaction solution and extraction was performed with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (solvent: n-hexane/ethyl acetate) to obtain the title compound (564 mg, 27% yield).

Workup

  1. temperaturethe mixture was heated
  2. customthe reaction
  3. temperatureto maintain
  4. temperaturereflux
  5. stirringAfter stirring the mixture for 15 minutes
  6. customapproximately 6 ml of the obtained reaction solution
  7. stirringstirring
  8. washThe organic layer was washed with saturated brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. distillationthe solvent was distilled off under reduced pressure
  11. customThe residue was purified by silica gel column chromatography (solvent: n-hexane/ethyl acetate)

Sources & evidence

ORD record
ord-0aba446fbc9d4559acc26353a3a44f97
Source dataset
uspto-grants-2006_02
Patent number
US06995144B2

Reaction notes

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