Sodium Thiosulfate → Ethyl 1-(3-(2-thienyl)propionyl)-3-piperidinecarboxylate

HRID 432808Notes

Reaction equation

HRID 432808 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH:6]=[CH:7][C:8]([N:10]1[CH2:15][CH2:14][CH2:13][CH:12]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH2:11]1)=[O:9].O.NN.I([O-])(=O)(=O)=O.[Na+].S([O-])([O-])(=O)=S.[Na+].[Na+]>CS(C)=O.S([O-])([O-])(=O)=O.[Cu+2].C(O)(=O)C.O.ClCCl>[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][CH2:7][C:8]([N:10]1[CH2:15][CH2:14][CH2:13][CH:12]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH2:11]1)=[O:9]

Participants

10

Reactant 4

HCID 24477Sodium ThiosulfateHCID 24654Hydrazine hydrate (1:1)HCID 23667635Sodium periodateHCID 54520739Ethyl 1-(3-(2-thienyl)acrylyl)-3-piperidinecarboxylate

Product 1

HCID 18760281Ethyl 1-(3-(2-thienyl)propionyl)-3-piperidinecarboxylateYield 33.9%

Reagents, catalysts & solvents 5

HCID 176Acetic AcidCatalystHCID 24462Copper SulfateCatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Ethyl 1-(3-(2-thienyl)acrylyl)-3-piperidinecarboxylate (404.1 mg; 1.38 mmol) was suspended in dimethyl sulfoxide (8 ml). The suspension was treated with hydrazine hydrate (1.7 ml; 54.7 mmol), saturated aqueous copper sulfate solution (6 drops), and glacial acetic acid (6 drops). This mixture was then stirred at ambient temperature and sodium periodate (1.47 g; 6.87 mmol) in water (20 ml) was added dropwise. After stirring an additional 1 hour, the mixture was taken up between aqueous 5% sodium thiosulfate and dichloromethane. The dichloromethane was separated, dried with anhydrous potassium carbonate, and evaporated at ambient temperature under reduced pressure. The crude product was purified by reverse phase chromatography on a C18 column, eluting with 30:70 to 40:60 acetonitrile:water as a step gradient, giving ethyl 1-(3-(2-thienyl)propionyl)-3-piperidinecarboxylate (138 mg) as a colorless oil. MS m/z (positive ion) 296 (MH+; 100).

Workup

  1. stirringAfter stirring an additional 1 hour
  2. customThe dichloromethane was separated
  3. dry with materialdried with anhydrous potassium carbonate
  4. customevaporated at ambient temperature under reduced pressure
  5. customThe crude product was purified by reverse phase chromatography on a C18 column
  6. washeluting with 30:70 to 40:60 acetonitrile

Sources & evidence

ORD record
ord-c9ef6bf1c6b34bffa857fab1fd4863ec
Source dataset
uspto-grants-2003_12
Patent number
US06664271B1

Reaction notes

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