Trifluoroacetic acid → (R)-benzyl 2-isopropyl-3-oxopiperazine-1-carboxylate

HRID 1051809Notes

Reaction equation

HRID 1051809 reaction equation
[CH:1]([C@@H:4]1[C:9](=[O:10])[NH:8][CH:7]=[CH:6][N:5]1[C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12])([CH3:3])[CH3:2].[SiH](CC)(CC)CC.C(O)(C(F)(F)F)=O>ClCCCl>[CH:1]([C@@H:4]1[C:9](=[O:10])[NH:8][CH2:7][CH2:6][N:5]1[C:11]([O:13][CH2:14][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)=[O:12])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 89827917(R)-benzyl 2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-carboxylate

Product 1

HCID 89827916(R)-benzyl 2-isopropyl-3-oxopiperazine-1-carboxylateYield 99.75%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a stirring solution of (R)-benzyl 2-isopropyl-3-oxo-3,4-dihydropyrazine-1(2H)-carboxylate (400 g, 1.46 mol) in DCE (2 L) was added Et3SiH (424 g, 3.65 mol) and TFA (665 g, 5.8 mol) at rt. The reaction was stirred under reflux for 36 h. After cooling to rt, the solution was concentrated to remove the solvent. The residue was diluted with EtOAc (2 L), and added slowly into stirring cooled sat. aq. NaHCO3 (2 L) to make sure that the pH >8. The mixture was extracted with EtOAc (2×2.5 L). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated to give (R)-benzyl 2-isopropyl-3-oxopiperazine-1-carboxylate (402 g, yield 99.75%), which was used for next step without further purification. LC-MS m/z 276.9 [M+H]+. 1H NMR (DMSO-d6 400 MHz): δ 7.93 (s, 1H), 7.39-7.31 (m, 5H), 5.09 (s, 2H), 4.06-4.01 (m, 1H), 3.99-3.92 (m, 1H), 3.23-3.14 (m, 3H), 2.20-2.12 (m, 1H), 0.96-0.94 (m, 3H), 0.85 (d, J=6.0 Hz, 3H).

Workup

  1. temperatureunder reflux for 36 h
  2. concentrationthe solution was concentrated
  3. customto remove the solvent
  4. additionThe residue was diluted with EtOAc (2 L)
  5. additionadded slowly
  6. stirringinto stirring
  7. temperaturecooled sat. aq. NaHCO3 (2 L)
  8. extractionThe mixture was extracted with EtOAc (2×2.5 L)
  9. washThe combined organic layers were washed with brine
  10. dry with materialdried over anhydrous Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-ea36d3ef67344bd9a255d75d8c8439e1
Source dataset
uspto-grants-2016_07
Patent number
US09388190B2

Reaction notes

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