1-Methyl-4-piperidone → HCID 12851360, compound

HRID 1065497Notes

Reaction equation

HRID 1065497 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:14])=[C:6]([CH:13]=1)[CH2:7][N:8]1[CH:12]=[CH:11][CH:10]=[CH:9]1.C([Li])CCC.[CH3:20][N:21]1[CH2:26][CH2:25][C:24](=[O:27])[CH2:23][CH2:22]1>C1COCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:14])=[C:6]([CH:7]([N:8]2[CH:12]=[CH:11][CH:10]=[CH:9]2)[C:24]2([OH:27])[CH2:25][CH2:26][N:21]([CH3:20])[CH2:22][CH2:23]2)[CH:13]=1

Participants

5

Reactant 3

HCID 740491-Methyl-4-piperidoneHCID 12851359HCID 12851359, compoundHCID 178418339Butyllithium

Product 1

HCID 12851360HCID 12851360, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-80 °C

Procedure

To a solution of 1-(5-chloro-2-fluorobenzyl)pyrrole of Example XVIIIa (15 g, 72 mmole) in 100 ml THF, cooled to -80° C., is added a solution of n-butyllithium (2.5 M in hexane 75 mmole, 30 ml) over a period of ten minutes. The mixture is stirred at -80° C. for one hour, then at -50° C. for 15 minutes. The mixture is again cooled to -80° C., then a solution of 1-methyl-4-piperidone (8.1 g, 72 mmole) in 50 ml THF is added. After stirring at ambient temperature for two hours, the mixture is poured over 500 ml ice water and is extracted with ether. The organic layer is extracted with diluted HCl. The aqueous acidic extract is then basified with sodium carbonate and extracted with ether. The organic extracts are washed twice with water and dried (saturated NaCl, anhydrous MgSO4). The solution is filtered and concentrated to a solid (21 g, 90%, m.p. 110°-115° C.) of which 4 g is recrystallized from hexanes to yield crystals, m.p. 124°-125° C. of 4-[(5-chloro-2-fluorophenyl)-(1-pyrryl)methyl]-1-methyl-4-piperidinol.

Workup

  1. customcooled to -80° C.
  2. waitat -50° C. for 15 minutes
  3. temperatureThe mixture is again cooled to -80° C.
  4. stirringAfter stirring at ambient temperature for two hours
  5. extractionis extracted with ether
  6. extractionThe organic layer is extracted with diluted HCl
  7. extractionThe aqueous acidic extract
  8. extractionextracted with ether
  9. washThe organic extracts are washed twice with water
  10. dry with materialdried (saturated NaCl, anhydrous MgSO4)
  11. filtrationThe solution is filtered
  12. concentrationconcentrated to a solid (21 g, 90%, m.p. 110°-115° C.) of which 4 g
  13. customis recrystallized from hexanes

Sources & evidence

ORD record
ord-318ea903b18e46de93a70fddc170e9e1
Source dataset
uspto-grants-1982_05
Patent number
US04329464

Reaction notes

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