Thiophene-3-carboxylic acid → Ethyl 1-(3-thiophenecarbonyl)-3-piperidinecarboxylate

HRID 432790Notes

Reaction equation

HRID 432790 reaction equation
[S:1]1[CH:5]=[CH:4][C:3]([C:6]([OH:8])=O)=[CH:2]1.Cl.CN(C)CCCN=C=NCC.[NH:21]1[CH2:31][CH2:30][CH2:29][CH:23]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:22]1>ClCCl>[S:1]1[CH:5]=[CH:4][C:3]([C:6]([N:21]2[CH2:31][CH2:30][CH2:29][CH:23]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:22]2)=[O:8])=[CH:2]1

Participants

5

Reactant 3

HCID 6918Thiophene-3-carboxylic acidHCID 98969Ethyl nipecotateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 12114708Ethyl 1-(3-thiophenecarbonyl)-3-piperidinecarboxylateYield 19.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Commercially available 3-thiophene carboxylic acid (166.5 mg; 1.30 mmol) was suspended in dichloromethane (7 ml), and commercially available 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (252.8 mg; 1.32 mmol) was added. This mixture was allowed to stir at ambient temperature for 1 hour. Ethyl nipecotate (201 μl; 1.3 mmol) was then added, and stirring was continued for approximately 18 hours. The reaction mixture was then diluted with fresh dichloromethane and washed with water. The dichloromethane was dried with anhydrous potassium carbonate and evaporated at ambient temperature under reduced pressure. The crude material was purified by high-vacuum distillation at approximately 225° C./0.1 torr, and further by chromatography on silica, eluting with 50% ethyl acetate in hexane, giving ethyl 1-(3-thiophenecarbonyl)-3-piperidinecarboxylate (66.3 mg) as a colorless oil. MS m/z (positive ion) 268 (MH+; 100).

Workup

  1. stirringstirring
  2. waitwas continued for approximately 18 hours
  3. washwashed with water
  4. dry with materialThe dichloromethane was dried with anhydrous potassium carbonate
  5. customevaporated at ambient temperature under reduced pressure
  6. distillationThe crude material was purified by high-vacuum distillation at approximately 225° C./0.1 torr
  7. washfurther by chromatography on silica, eluting with 50% ethyl acetate in hexane

Sources & evidence

ORD record
ord-9a95a3adc07541328b54435380b7407a
Source dataset
uspto-grants-2003_12
Patent number
US06664271B1

Reaction notes

Loading…