1-Bromo-4-fluorobenzene → alpha,alpha-Bis(4-fluorophenyl)-1-(phenylsulfonyl)-4-piperidinemethanol

HRID 1709808Notes

Reaction equation

HRID 1709808 reaction equation
[Mg].Br[C:3]1[CH:8]=[CH:7][C:6]([F:9])=[CH:5][CH:4]=1.C(O[C:13]([CH:15]1[CH2:20][CH2:19][N:18]([S:21]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)(=[O:23])=[O:22])[CH2:17][CH2:16]1)=[O:14])C.[Cl-].[NH4+]>O1CCCC1>[F:9][C:6]1[CH:7]=[CH:8][C:3]([C:13]([C:3]2[CH:8]=[CH:7][C:6]([F:9])=[CH:5][CH:4]=2)([CH:15]2[CH2:16][CH2:17][N:18]([S:21]([C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)(=[O:22])=[O:23])[CH2:19][CH2:20]2)[OH:14])=[CH:4][CH:5]=1

Participants

6

Reactant 4

HCID 99931-Bromo-4-fluorobenzeneHCID 25517Ammonium ChlorideHCID 257103Ethyl 1-(phenylsulfonyl)piperidine-4-carboxylateHCID 5462224Magnesium

Product 1

HCID 14407073alpha,alpha-Bis(4-fluorophenyl)-1-(phenylsulfonyl)-4-piperidinemethanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of 33.78 g (1.39 mole) of magnesium trimmings in 1 liter of tetrahydrofuran (dried over molecular sieves 5A) under an atmosphere of nitrogen and cooled in an ice bath was added dropwise a solution of 243.25 g (1.39 mole) of p-bromoflurobenzene in 150 of tetrahydrofuran. The mixture was stirred for 2 hr after the addition was completed. To this mixture was added 103 g (0.346 mole) of 1-(phenylsulfonyl)-4-piperidinecarboxylic acid ethyl ester as a solid, and the solution was stirred at ambient temperature for 5 hr. The reaction mixture was poured into an icy aqueous solution of ammonium chloride. The phases was separated, and the solvent was removed in vacuo from the organic phase. The residue was partitioned between methylene chloride and dilute sodium hydroxide. The methylene chloride solution was dried over magnesium sulfate and was reduced in vacuo to ≃1 liter volume. The title compound was obtained by adding hexane and cooling, recrystallizing and the precipitate from ethyl acetate and hexane and drying the solid under high vacuum at 130° C. for 45 min at which time the product had partially melted, m.p. 142.5°-144° C.

Workup

  1. temperaturecooled in an ice bath
  2. additionafter the addition
  3. stirringthe solution was stirred at ambient temperature for 5 hr
  4. customThe phases was separated
  5. customthe solvent was removed in vacuo from the organic phase
  6. customThe residue was partitioned between methylene chloride and dilute sodium hydroxide
  7. dry with materialThe methylene chloride solution was dried over magnesium sulfate

Sources & evidence

ORD record
ord-497ee5c949e44a4899256ac7ff2e4dd2
Source dataset
uspto-grants-1990_08
Patent number
US04950674

Reaction notes

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