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

HRID 1482950Notes

Reaction equation

HRID 1482950 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 cooled to rt, the solution was concentrated to remove the solvent. The residue was diluted with EtOAc (2 L), and it was added slowly into a 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, filter 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), and it
  5. additionwas added slowly into a stirring
  6. temperaturecooled sat. aq. NaHCO3 (2 L)
  7. extractionThe mixture was extracted with EtOAc (2×2.5 L)
  8. washThe combined organic layers were washed with brine
  9. dry with materialdried over anhydrous Na2SO4
  10. filtrationfilter
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-891dc0b9646c49afae06bda4a8cb9016
Source dataset
uspto-grants-2016_08
Patent number
US09416135B2

Reaction notes

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