4-Bromobiphenyl → 1-Benzyl-4-hydroxy4-(4-phenylphenyl)piperidine

HRID 2299030Notes

Reaction equation

HRID 2299030 reaction equation
C([Li])CCC.CCCCCC.Br[C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[CH:15][CH:14]=1.[CH2:25]([N:32]1[CH2:37][CH2:36][C:35](=[O:38])[CH2:34][CH2:33]1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>O1CCCC1>[CH2:25]([N:32]1[CH2:37][CH2:36][C:35]([OH:38])([C:13]2[CH:18]=[CH:17][C:16]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[CH:15][CH:14]=2)[CH2:34][CH2:33]1)[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1

Participants

6

Reactant 4

HCID 71014-BromobiphenylHCID 8058HexaneHCID 192201-Benzyl-4-piperidoneHCID 178418339Butyllithium

Product 1

HCID 183796201-Benzyl-4-hydroxy4-(4-phenylphenyl)piperidineYield 80.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A 1.6M solution of n-butyllithium in hexane (39 ml, 63 mmol) was added to a stirred solution of 4-bromobiphenyl (11.7 g, 50 mmol) in anhydrous tetrahydrofuran (50 ml), under nitrogen, at about −50° C., whilst ensuring that the reaction temperature was kept below −40° C. After a further 1 hour, a solution of 1-benzyl-4-oxopiperidine (10.4 g, 55 mmol) in anhydrous tetrahydrofuran (30 ml) was added at such a rate that the reaction temperature was maintained below −40° C. The cooling bath was then removed and, after a further 1 hour, the reaction mixture was partitioned between dichloromethane (400 ml) and brine (200 ml). The organic phase was separated, washed with water, dried (MgSO4) and evaporated under reduced pressure, then the residue crystallised from ethyl acetate to provide the title compound (13.9 g) as a colourless solid. δ(DMSOd6): 1.80 (d,2H), 2.52 (m,2H), 3.24 (m,4H), 4.33 (d,2H), 7.28-7.75 (m,14H), 11.30 (brs, 1H).

Workup

  1. customwas kept below −40° C
  2. temperaturewas maintained below −40° C
  3. customThe cooling bath was then removed and, after a further 1 hour
  4. customthe reaction mixture was partitioned between dichloromethane (400 ml) and brine (200 ml)
  5. customThe organic phase was separated
  6. washwashed with water
  7. dry with materialdried (MgSO4)
  8. customevaporated under reduced pressure
  9. customthe residue crystallised from ethyl acetate

Sources & evidence

ORD record
ord-2953d067d3e84b5e8b910540555c593c
Source dataset
uspto-grants-2002_12
Patent number
US06495568B1

Reaction notes

Loading…