Iodine → alpha,alpha-Bis(4-fluorophenyl)-1-(phenylmethyl)-4-piperidinemethanol

HRID 1709806Notes

Reaction equation

HRID 1709806 reaction equation
[Mg].II.Br[C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][CH:6]=1.C(O[C:15]([CH:17]1[CH2:22][CH2:21][N:20]([CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:19][CH2:18]1)=[O:16])C.[Cl-].[NH4+]>O1CCCC1>[F:11][C:8]1[CH:9]=[CH:10][C:5]([C:15]([C:5]2[CH:10]=[CH:9][C:8]([F:11])=[CH:7][CH:6]=2)([CH:17]2[CH2:18][CH2:19][N:20]([CH2:23][C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)[CH2:21][CH2:22]2)[OH:16])=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 807IodineHCID 99931-Bromo-4-fluorobenzeneHCID 25517Ammonium ChlorideHCID 90423Ethyl 1-benzylpiperidine-4-carboxylateHCID 5462224Magnesium

Product 1

HCID 13519964alpha,alpha-Bis(4-fluorophenyl)-1-(phenylmethyl)-4-piperidinemethanolYield 51%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a 6.08 g (0.25 mole) of magnesium turnings and an iodine crystal in 600 ml of dry tetrahydrofuran and under an atmosphere of nitrogen was added, dropwise, a solution of p-bromofluorobenzene in 125 ml of tetrahydrofuran. The temperature of the reaction was kept below 10° C. by cooling in an ice-methanol bath. The mixture was stirred at room temperature for 1.5 hours. A solution of 24.7 g (0.10 mole) of 1-(phenylmethyl)-4-piperidinecarboxylic acid ethyl ester in tetrahydrofuran was added, and the mixture was stirred at room temperature for 17 hours. The reaction was poured into an icy, aqueous solution of ammonium chloride, and the resulting solution was extracted with methylene chloride. The methylene chloride solution was extracted with dilute sodium hydroxide and was dried over magnesium sulfate. The solvent was removed in vacuo to give an oil. This was crystallized from ether-hexane to give 19.87 g (51%) of the title compound, m.p. 113°-15° C.

Workup

  1. customwas kept below 10° C.
  2. temperatureby cooling in an ice-methanol bath
  3. stirringthe mixture was stirred at room temperature for 17 hours
  4. extractionthe resulting solution was extracted with methylene chloride
  5. extractionThe methylene chloride solution was extracted with dilute sodium hydroxide
  6. dry with materialwas dried over magnesium sulfate
  7. customThe solvent was removed in vacuo
  8. customto give an oil
  9. customThis was crystallized from ether-hexane

Sources & evidence

ORD record
ord-4a9c49eca6f241338d548648208c9378
Source dataset
uspto-grants-1990_08
Patent number
US04950674

Reaction notes

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