2-Thiophenecarbonyl chloride → Tert-butyl 4-(5-(2-thienyl)-1,2,4-oxadiazol-3-yl)piperazine-1-carboxylate

HRID 888203Notes

Reaction equation

HRID 888203 reaction equation
[OH:1][NH:2][C:3](=[NH:17])[N:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1.[S:18]1[CH:22]=[CH:21][CH:20]=[C:19]1[C:23](Cl)=O.CCN(C(C)C)C(C)C>C(Cl)Cl>[S:18]1[CH:22]=[CH:21][CH:20]=[C:19]1[C:23]1[O:1][N:2]=[C:3]([N:4]2[CH2:5][CH2:6][N:7]([C:10]([O:12][C:13]([CH3:14])([CH3:16])[CH3:15])=[O:11])[CH2:8][CH2:9]2)[N:17]=1

Participants

5

Reactant 3

HCID 789282-Thiophenecarbonyl chlorideHCID 81531DiisopropylethylamineHCID 178452346tert-butyl 4-(N-hydroxyamidino)-piperazine-1-carboxylate

Product 1

HCID 58487964Tert-butyl 4-(5-(2-thienyl)-1,2,4-oxadiazol-3-yl)piperazine-1-carboxylateYield 20%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a cold (0° C.) solution of tert-butyl 4-[(hydroxyamino)(imino)methyl]piperazine-1-carboxylate (8 g, 32.7 mmol) in anhydrous DCM (150 mL) was added thiophene-2-carbonyl chloride (4.8 g, 32.7 mmol) followed by DIEA (7.2 mL, 39.2 mmol). The reaction mixture was stirred at RT for 12 hours and then filtered. The filtrate was evaporated and the residue was refluxed in pyridine (100 mL) for 3 hours. The solvent was removed under vacuum and the residue was dissolved in DCM. The organic layer was washed with a 10% aq. solution of sodium bicarbonate, water, brine and dried. The solvent was concentrated and the residue was purified by chromatography (Pet. Ether/EtOAc 7/3) to give 2.2 g (20%) of The title compound as a solid. TLC-Pet ether/EtOAc (9/1): Rf=0.75. HPLC purity>97%.

Workup

  1. filtrationfiltered
  2. customThe filtrate was evaporated
  3. temperaturethe residue was refluxed in pyridine (100 mL) for 3 hours
  4. customThe solvent was removed under vacuum
  5. dissolutionthe residue was dissolved in DCM
  6. washThe organic layer was washed with a 10% aq. solution of sodium bicarbonate, water, brine
  7. customdried
  8. concentrationThe solvent was concentrated
  9. customthe residue was purified by chromatography (Pet. Ether/EtOAc 7/3)

Sources & evidence

ORD record
ord-c015abd082ed4c13a5b11d2757071805
Source dataset
uspto-grants-2012_08
Patent number
US08247437B2

Reaction notes

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