Diethyl Ether → 1-Methyl-4-phenylpiperidin-4-ol

HRID 2163135Notes

Reaction equation

HRID 2163135 reaction equation
CCOCC.[Li].Br[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[CH3:14][N:15]1[CH2:20][CH2:19][C:18](=[O:21])[CH2:17][CH2:16]1>C(Cl)Cl.O>[CH3:14][N:15]1[CH2:20][CH2:19][C:18]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)([OH:21])[CH2:17][CH2:16]1

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 7961Bromobenzene2×HCID 740491-Methyl-4-piperidoneHCID 3028194Lithium

Product 1

HCID 786701-Methyl-4-phenylpiperidin-4-ol

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Anhydrous ether (1900 ml) is placed, under nitrogen, in a previously dried 5 liter 3-necked flask fitted with dropping funnel, reflux condenser and magnetic stirrer. Lithium (28.4 g, 4.1 g. at.) is added together with 20 ml bromobenzene (20 ml). The mixture is heated at reflux temperature until a reaction commences. Heating is discontinued and a total of 312 g. (2.0 moles) bromobenzene is added dropwise during 0.5 hour. The mixture is stirred for a further 3 hours and the remaining traces of lithium are removed. The solution is cooled to 0° C. and 1-methyl-4-piperidone (161 g, 1.42 moles) is added over a 0.5 hour period. The mixture is stirred for a further 2 hours at room temperature, cooled to 0° C. and water (500 ml) is added. The mixture is transferred to a separating funnel. Methylene chloride is added to redissolve the precipitate which formed and the aqueous layer is extracted with ether. The combined ether extracts are dried over Na2SO4, evaporated and crystallized from methylene chloride-pentane to give the title compound, mp 110°-112° C. (S. M. Elreain and J. C. Safranski, Jr., supra, reported bp 128°-130° C./0.9mm).

Workup

  1. customfitted
  2. temperaturereflux condenser and magnetic stirrer
  3. temperatureThe mixture is heated
  4. temperatureat reflux temperature
  5. customuntil a reaction commences
  6. temperatureHeating
  7. customthe remaining traces of lithium are removed
  8. stirringThe mixture is stirred for a further 2 hours at room temperature
  9. temperaturecooled to 0° C.
  10. customThe mixture is transferred to a separating funnel
  11. dissolutionto redissolve the precipitate which
  12. customformed
  13. extractionthe aqueous layer is extracted with ether
  14. dry with materialThe combined ether extracts are dried over Na2SO4
  15. customevaporated
  16. customcrystallized from methylene chloride-pentane

Sources & evidence

ORD record
ord-0a7478eab58c42d2a5853b539b6116b7
Source dataset
uspto-grants-1979_01
Patent number
US04132710

Reaction notes

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