HCID 86604426, compound → HCID 22128446, compound

HRID 1858694Notes

Reaction equation

HRID 1858694 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH:13]([O:14]C(OCC(Cl)(Cl)Cl)=O)[CH2:12][N:11](C(OCC(Cl)(Cl)Cl)=O)[CH2:10][CH:9]2[CH2:31][CH2:32][CH3:33])=[CH:4][CH:3]=1>C(O)(=O)C.[Zn]>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH:9]([CH2:31][CH2:32][CH3:33])[CH2:10][NH:11][CH2:12][CH:13]2[OH:14])=[CH:4][CH:3]=1

Participants

4

Reactant 1

HCID 86604426HCID 86604426, compound

Product 1

HCID 22128446HCID 22128446, compoundYield 55%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalyst2×HCID 176Acetic AcidSolvent

Procedure

A mixture of 13.05 g (21.6 mmol) of 2,2,2-trichloro-ethyl (3RS,4SR,5SR)-4-(4-chloro-phenyl)-3-propyl-5-(2,2,2-trichloro-ethoxycarbonyloxy)-piperidine-1-carboxylate and 14.5 g of zinc in 200 ml of glacial acetic acid was treated in an ultrasound bath for 15 hours. In order to complete the reaction, a further 5 g of zinc were subsequently added and the mixture was left in the ultrasound bath for a further 5 hours. For the working-up, the zinc was filtered off under suction, the residue was rinsed with glacial acetic acid and the solution was evaporated to dryness under reduced pressure. The residue was partitioned between 1N NaOH and ethyl acetate, the separated aqueous phase was then again extracted with ethyl acetate and finally the combined organic phases were evaporated under reduced pressure. The crude product obtained was crystallized from diethyl ether and gave 3.0 g (55% of theory) of (3RS,4RS,5SR)-4-(4-chloro-phenyl)-5-propyl-piperidin-3-ol as colourless crystals; MS: 253 (M)+. For purification, the mother liquor was chromatographed on silica gel using a 90:10:0.1 mixture of methylene chloride, methanol and ammonia as the eluent. There were obtained a further 1.1 g (20% of theory) of (3RS,4RS,5SR)-4-(4-chloro-phenyl)-5-propyl-piperidin-3-ol.

Workup

  1. additionwas treated in an ultrasound bath for 15 hours
  2. customthe reaction
  3. filtrationthe zinc was filtered off under suction
  4. washthe residue was rinsed with glacial acetic acid
  5. customthe solution was evaporated to dryness under reduced pressure
  6. customThe residue was partitioned between 1N NaOH and ethyl acetate
  7. extractionthe separated aqueous phase was then again extracted with ethyl acetate
  8. customfinally the combined organic phases were evaporated under reduced pressure
  9. customThe crude product obtained
  10. customwas crystallized from diethyl ether

Sources & evidence

ORD record
ord-42c75de8bfb6461f862aac220f54cd96
Source dataset
uspto-grants-2000_11
Patent number
US06150526

Reaction notes

Loading…