2-Fluoroethyl p-Toluenesulfonate → 1-Tert-butoxycarbonyl-4-(2-fluoroethyl)-3-oxopiperazine

HRID 1166012Notes

Reaction equation

HRID 1166012 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][C:10](=[O:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC(C)([O-])C.[K+].CC1C=CC(S(O[CH2:32][CH2:33][F:34])(=O)=O)=CC=1>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:32][CH2:33][F:34])[C:10](=[O:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 2560192-Fluoroethyl p-ToluenesulfonateHCID 3157178Tert-butyl 3-oxopiperazine-1-carboxylateHCID 23665647Potassium tert-butoxide

Product 1

HCID 227164681-Tert-butoxycarbonyl-4-(2-fluoroethyl)-3-oxopiperazine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1-t-Butoxycarbonyl-3-oxopiperazine (21.6 g) is dissolved in dry DMF (500 ml) and potassium t-butoxide (24.2 g) is added. The mixture is stirred at 20-25° for 30 minutes, then 1-(4-methylphenylsulfonyloxy)-2-fluoroethane (J. Med. Chem., 23(9), 985-90 (1980), 25.9 g) is added and stirring continued at the same temperature for 24 hours. The solvent is removed and the residue partitioned between ethyl acetate and water. The organic phase is washed with water and concentrated. The residue is dissolved in isopropanol and diluted with iso-hexane forming a precipitate which is removed by filtration. The mixture is chromatographed (silica; eluting with a gradient increasing in polarity from 0 to 50% isopropanol in iso-hexane) to give 1-t-butoxycarbonyl-4-(2-fluoroethyl)-3-oxopiperazine.

Workup

  1. stirringstirring
  2. waitcontinued at the same temperature for 24 hours
  3. customThe solvent is removed
  4. customthe residue partitioned between ethyl acetate and water
  5. washThe organic phase is washed with water
  6. concentrationconcentrated
  7. dissolutionThe residue is dissolved in isopropanol
  8. additiondiluted with iso-hexane forming a precipitate which
  9. customis removed by filtration
  10. customThe mixture is chromatographed (silica
  11. washeluting with
  12. temperaturea gradient increasing in polarity from 0 to 50% isopropanol in iso-hexane)

Sources & evidence

ORD record
ord-621c5abe763045aeaa6ef457cf15fbb7
Source dataset
uspto-grants-2003_09
Patent number
US06613349B2

Reaction notes

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