Triethylamine → HCID 3217652, compound

HRID 2227158Notes

Reaction equation

HRID 2227158 reaction equation
[O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[NH:5][CH:4]=[C:3]1[C:12]([OH:14])=O.C(N(CC)CC)C.ClC(OCC)=O.[CH2:28]([NH2:34])[CH:29]1[O:33][CH2:32][CH2:31][CH2:30]1.[Cl-].[NH4+]>CN(C=O)C.C1COCC1>[CH2:28]([NH:34][C:12]([C:3]1[C:2](=[O:1])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[NH:5][CH:4]=1)=[O:14])[CH:29]1[O:33][CH2:32][CH2:31][CH2:30]1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 25517Ammonium ChlorideHCID 2208754-Quinolone-3-carboxylic acidHCID 253298Tetrahydrofurfurylamine

Product 1

HCID 3217652HCID 3217652, compoundYield 47.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-oxo-1,4-dihydro-quinoline-3-carboxylic acid (95 mg, 0.5 mmol) in a 4:1 mixture of THF:DMF (2.5 mL) and triethylamine (146 μL, 1.05 mmol) at 0° C. is added ethyl chloroformate (98 μL, 1.03 mmol). The reaction mixture is allowed to stir for 1 h before tetrahydrofurfurylamine (155 μL, 1.5 mmol) is added. The reaction mixture is stirred for ¾ h and then allowed to warm to ambient temperature for 20 h. The mixture is subsequently poured into aqueous ammonium chloride, the THF is removed in vacuo, and the mixture is extracted with ethyl acetate. The organic layer is dried (Na2SO4), filtered and concentrated. The residue is treated with 1N NaOH (2 mL) and ethanol (0.5 mL) at reflux for 1 h. The reaction mixture is cooled, diluted with aqueous ammonium chloride and extracted 2× with dichloromethane. The combined organic layers are dried (Na2SO4), filtered, and concentrated to give 65 mg of N-tetrahydrofurfuryl 4-oxo-1,4-dihydro-quinoline-3-carboxamide (compound 1) as a cream solid; m.p. 205-209° C.

Workup

  1. additionis added
  2. customthe THF is removed in vacuo
  3. extractionthe mixture is extracted with ethyl acetate
  4. dry with materialThe organic layer is dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. additionThe residue is treated with 1N NaOH (2 mL) and ethanol (0.5 mL)
  8. temperatureat reflux for 1 h
  9. temperatureThe reaction mixture is cooled
  10. additiondiluted with aqueous ammonium chloride
  11. extractionextracted 2× with dichloromethane
  12. dry with materialThe combined organic layers are dried (Na2SO4)
  13. filtrationfiltered
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-392614c62790447f8f06f8f398f73579
Source dataset
uspto-grants-2002_07
Patent number
US06413956B1

Reaction notes

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