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

HRID 476924Notes

Reaction equation

HRID 476924 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 magnesium turnings (6.08 g, 0.25 mole) and an iodine crystal in 600 ml of dry tetrahydrofuran (THF) (distilled from lithium aluminum hydride) and under an atmosphere of nitrogen was added dropwise a solution of p-bromofluorobenzene in 125 ml of THF. The temperature of the reaction mixture was kept below 10° C. by cooling in an ice-methanol bath. The mixture was stirred at room temperature for 1.5 hr. A solution of 1-(phenylmethyl)-4-piperidinecarboxylic acid ethyl ester (24.7 g, 0.10 mole) in THF was added, and the mixture was stirred at room temperature for 17 hr. The reaction mixture was poured into an icy, aqueous solution of ammonium chloride, and the resulting solution was extracted with methylene chloride. The solution was extracted with dilute sodium hydroxide and was dried (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 title compound, m.p. 113°-115° 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 hr
  4. extractionthe resulting solution was extracted with methylene chloride
  5. extractionThe solution was extracted with dilute sodium hydroxide
  6. dry with materialwas dried (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-299dd4a7b864443c8c9fa9d13b02ffc3
Source dataset
uspto-grants-1989_12
Patent number
US04886794

Reaction notes

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