1-Bromo-3-chlorobenzene → 3-(3-Chlorophenyl)-1-(phenylmethyl)-3-piperidinol hydrochloride

HRID 359409Notes

Reaction equation

HRID 359409 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[CH:3]=1.[Mg].O1CCCC1.[C:15]1([CH2:21][N:22]2[CH2:27][CH2:26][CH2:25][C:24](=[O:28])[CH2:23]2)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>C(O)(=O)C>[ClH:8].[Cl:8][C:4]1[CH:3]=[C:2]([C:24]2([OH:28])[CH2:25][CH2:26][CH2:27][N:22]([CH2:21][C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH2:23]2)[CH:7]=[CH:6][CH:5]=1

Participants

6

Reactant 4

HCID 79281-Bromo-3-chlorobenzeneHCID 8028TetrahydrofuranHCID 966503-Piperidinone, 1-(phenylmethyl)-HCID 5462224Magnesium

Product 1

HCID 190955863-(3-Chlorophenyl)-1-(phenylmethyl)-3-piperidinol hydrochlorideYield 76%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a stirred and refluxed Grignard complex previously prepared starting from a mixture of 4.2 parts of 1-bromo-3-chlorobenzene, 5.4 parts of magnesium and 135 parts of tetrahydrofuran were added dropwise 19 parts of 1-(phenylmethyl)-3-piperidinone. Upon completion, stirring was continued for 1 hour at reflux temperature. After cooling, the reaction mixture was poured into ice water and 12.5 parts of acetic acid. The layers were separated. The aqueous phase was extracted with trichloromethane. The organic layer was washed with water, dried, filtered and evaporated. The residue was converted into the hydrochloride salt in 2-propanol. The salt was filtered off and dried, yielding 26 parts (76%) of 3-(3-chlorophenyl)-1-(phenylmethyl)-3-piperidinol hydrochloride (intermediate 27).

Workup

  1. temperaturerefluxed Grignard complex
  2. custompreviously prepared
  3. stirringUpon completion, stirring
  4. temperatureat reflux temperature
  5. temperatureAfter cooling
  6. customThe layers were separated
  7. extractionThe aqueous phase was extracted with trichloromethane
  8. washThe organic layer was washed with water
  9. customdried
  10. filtrationfiltered
  11. customevaporated
  12. filtrationThe salt was filtered off
  13. customdried

Sources & evidence

ORD record
ord-a077c131c37446cda95b2797740d3ca2
Source dataset
uspto-grants-1991_03
Patent number
US05001125

Reaction notes

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