Hydrochloric Acid → 1-Carbethoxy-4-hydroxy-4-[2-(4-methylphenylsulfanyl)phenyl]piperidine

HRID 2069163Notes

Reaction equation

HRID 2069163 reaction equation
[C:1]1([CH3:15])[CH:6]=[CH:5][C:4]([S:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2Br)=[CH:3][CH:2]=1.[Li]CCCC.CCCCCC.[C:27]([N:32]1[CH2:37][CH2:36][C:35](=[O:38])[CH2:34][CH2:33]1)([O:29][CH2:30][CH3:31])=[O:28].Cl>CCCCCCC.C1COCC1>[OH:38][C:35]1([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[S:7][C:4]2[CH:5]=[CH:6][C:1]([CH3:15])=[CH:2][CH:3]=2)[CH2:34][CH2:33][N:32]([C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH2:37][CH2:36]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8058HexaneHCID 34767Ethyl 4-oxo-1-piperidinecarboxylateHCID 21864904(2-Bromophenyl)(p-tolyl)sulfaneHCID 178418339Butyllithium

Product 1

HCID 452583081-Carbethoxy-4-hydroxy-4-[2-(4-methylphenylsulfanyl)phenyl]piperidine

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8900HeptaneSolvent

Procedure

In a stirred reactor under nitrogen cover 2-(4-tolylsulfanyl)-phenyl bromide (600 g, 2.15 mol) was suspended in heptane (4.5 L). At room temperature 10M BuLi in hexane (235 mL, 2.36 mol) was added over 10 minutes. Only a small exotherm was noticed. The suspension was stirred for 1 hour at ambient temperature and then cooled down to −40° C. 1-Carbethoxy-4-piperidone (368 g, 2.15 mol) dissolved in THF (1.5 L) was added at a rate not faster than the reaction temperature was kept below −40° C. When the reaction has gone to completion, it was warmed to 0° C. and 1M HCl (1 L) was added keeping the temperature below 10° C. The acid aqueous phase was separated and extracted with ethyl acetate (1 L). The organic phases were combined and extracted with sodium chloride solution (15%, 1 L). The organic phase was dried over sodium sulphate and evaporated to a semi crystalline mass. It was slurried with ethyl ether (250 mL) and filtered off. Dried in an vacuum oven at 40° C. until constant weight.

Workup

  1. customIn a stirred reactor under nitrogen cover
  2. temperaturecooled down to −40° C
  3. additionwas added at a rate not faster than the reaction temperature
  4. customwas kept below −40° C
  5. temperaturewas warmed to 0° C.
  6. customthe temperature below 10° C
  7. customThe acid aqueous phase was separated
  8. extractionextracted with ethyl acetate (1 L)
  9. extractionextracted with sodium chloride solution (15%, 1 L)
  10. dry with materialThe organic phase was dried over sodium sulphate
  11. customevaporated to a semi crystalline mass
  12. filtrationfiltered off
  13. customDried in an vacuum oven at 40° C. until constant weight

Sources & evidence

ORD record
ord-0d3588682943496da04506e3a05a659a
Source dataset
uspto-grants-2012_10
Patent number
US08299095B2

Reaction notes

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